diff --git a/CHANGELOG.md b/CHANGELOG.md
index 067791482e22..c40e79183f3e 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -3,6 +3,7 @@
 ### Features
 
 - `[expect, @jest/expect-utils]` Support custom equality testers ([#13654](https://github.com/facebook/jest/pull/13654))
+- `[jest-config]` Support using esbuild-register for loading TS configs ([#13742](https://github.com/facebook/jest/pull/13742))
 - `[jest-config, jest-worker]` Use `os.availableParallelism` if available to calculate number of workers to spawn ([#13738](https://github.com/facebook/jest/pull/13738))
 - `[@jest/globals, jest-mock]` Add `jest.replaceProperty()` that replaces property value ([#13496](https://github.com/facebook/jest/pull/13496))
 - `[jest-haste-map]` ignore Sapling vcs directories (`.sl/`) ([#13674](https://github.com/facebook/jest/pull/13674))
diff --git a/docs/Configuration.md b/docs/Configuration.md
index 0a071c26c713..11d77bed5de7 100644
--- a/docs/Configuration.md
+++ b/docs/Configuration.md
@@ -57,7 +57,7 @@ export default async (): Promise<Config> => {
 
 :::tip
 
-To read TypeScript configuration files Jest requires [`ts-node`](https://npmjs.com/package/ts-node). Make sure it is installed in your project.
+To read TypeScript configuration files Jest by default requires [`ts-node`](https://npmjs.com/package/ts-node). You can override this behavior by adding a `@jest-config-loader` docblock at the top of the file. Currently, [`ts-node`](https://npmjs.com/package/ts-node) and [`esbuild-register`](https://npmjs.com/package/esbuild-register) is supported. Make sure `ts-node` or the loader you specify is installed.
 
 :::
 
diff --git a/e2e/__tests__/readInitialOptions.test.ts b/e2e/__tests__/readInitialOptions.test.ts
index 9d2ba417eb4f..c8b798207261 100644
--- a/e2e/__tests__/readInitialOptions.test.ts
+++ b/e2e/__tests__/readInitialOptions.test.ts
@@ -46,58 +46,21 @@ describe('readInitialOptions', () => {
     expect(config).toEqual({jestConfig: 'jest.config.js', rootDir});
     expect(configPath).toEqual(configFile);
   });
-  test('should read a jest.config.js file', async () => {
-    const configFile = resolveFixture('js-config', 'jest.config.js');
-    const rootDir = resolveFixture('js-config');
-    const {config, configPath} = await proxyReadInitialOptions(undefined, {
-      cwd: rootDir,
-    });
-    expect(config).toEqual({jestConfig: 'jest.config.js', rootDir});
-    expect(configPath).toEqual(configFile);
-  });
-  test('should read a package.json file', async () => {
-    const configFile = resolveFixture('pkg-config', 'package.json');
-    const rootDir = resolveFixture('pkg-config');
-    const {config, configPath} = await proxyReadInitialOptions(undefined, {
-      cwd: rootDir,
-    });
-    expect(config).toEqual({jestConfig: 'package.json', rootDir});
-    expect(configPath).toEqual(configFile);
-  });
-  test('should read a jest.config.ts file', async () => {
-    const configFile = resolveFixture('ts-config', 'jest.config.ts');
-    const rootDir = resolveFixture('ts-config');
-    const {config, configPath} = await proxyReadInitialOptions(undefined, {
-      cwd: rootDir,
-    });
-    expect(config).toEqual({jestConfig: 'jest.config.ts', rootDir});
-    expect(configPath).toEqual(configFile);
-  });
-  test('should read a jest.config.mjs file', async () => {
-    const configFile = resolveFixture('mjs-config', 'jest.config.mjs');
-    const rootDir = resolveFixture('mjs-config');
-    const {config, configPath} = await proxyReadInitialOptions(undefined, {
-      cwd: rootDir,
-    });
-    expect(config).toEqual({jestConfig: 'jest.config.mjs', rootDir});
-    expect(configPath).toEqual(configFile);
-  });
-  test('should read a jest.config.json file', async () => {
-    const configFile = resolveFixture('json-config', 'jest.config.json');
-    const rootDir = resolveFixture('json-config');
-    const {config, configPath} = await proxyReadInitialOptions(undefined, {
-      cwd: rootDir,
-    });
-    expect(config).toEqual({jestConfig: 'jest.config.json', rootDir});
-    expect(configPath).toEqual(configFile);
-  });
-  test('should read a jest config exporting an async function', async () => {
-    const configFile = resolveFixture('async-config', 'jest.config.js');
-    const rootDir = resolveFixture('async-config');
+  test.each([
+    ['js-config', 'jest.config.js'],
+    ['pkg-config', 'package.json'],
+    ['ts-node-config', 'jest.config.ts'],
+    ['ts-esbuild-register-config', 'jest.config.ts'],
+    ['mjs-config', 'jest.config.mjs'],
+    ['json-config', 'jest.config.json'],
+    ['async-config', 'jest.config.js'],
+  ])('should read %s/%s file', async (directory: string, filename: string) => {
+    const configFile = resolveFixture(directory, filename);
+    const rootDir = resolveFixture(directory);
     const {config, configPath} = await proxyReadInitialOptions(undefined, {
       cwd: rootDir,
     });
-    expect(config).toEqual({jestConfig: 'async-config', rootDir});
+    expect(config).toEqual({jestConfig: filename, rootDir});
     expect(configPath).toEqual(configFile);
   });
 
diff --git a/e2e/read-initial-options/async-config/jest.config.js b/e2e/read-initial-options/async-config/jest.config.js
index 00df2a4f3837..6747ae8b570a 100644
--- a/e2e/read-initial-options/async-config/jest.config.js
+++ b/e2e/read-initial-options/async-config/jest.config.js
@@ -6,6 +6,6 @@
  */
 module.exports = async function () {
   return {
-    jestConfig: 'async-config',
+    jestConfig: 'jest.config.js',
   };
 };
diff --git a/e2e/read-initial-options/ts-esbuild-register-config/jest.config.ts b/e2e/read-initial-options/ts-esbuild-register-config/jest.config.ts
new file mode 100644
index 000000000000..9b003d380264
--- /dev/null
+++ b/e2e/read-initial-options/ts-esbuild-register-config/jest.config.ts
@@ -0,0 +1,15 @@
+/**
+ * Copyright (c) Facebook, Inc. and its affiliates. All Rights Reserved.
+ *
+ * This source code is licensed under the MIT license found in the
+ * LICENSE file in the root directory of this source tree.
+ *
+ * @jest-config-loader esbuild-register
+ */
+interface Config {
+  jestConfig: string;
+}
+
+export default {
+  jestConfig: 'jest.config.ts',
+} as Config;
diff --git a/e2e/read-initial-options/ts-config/jest.config.ts b/e2e/read-initial-options/ts-node-config/jest.config.ts
similarity index 81%
rename from e2e/read-initial-options/ts-config/jest.config.ts
rename to e2e/read-initial-options/ts-node-config/jest.config.ts
index bf05ee62de87..2575e19befb2 100644
--- a/e2e/read-initial-options/ts-config/jest.config.ts
+++ b/e2e/read-initial-options/ts-node-config/jest.config.ts
@@ -4,6 +4,10 @@
  * This source code is licensed under the MIT license found in the
  * LICENSE file in the root directory of this source tree.
  */
+interface Config {
+  jestConfig: string;
+}
+
 export default {
   jestConfig: 'jest.config.ts',
-};
+} as Config;
diff --git a/packages/jest-config/package.json b/packages/jest-config/package.json
index 0bdcc09d501e..292be0abdd6b 100644
--- a/packages/jest-config/package.json
+++ b/packages/jest-config/package.json
@@ -18,12 +18,16 @@
   },
   "peerDependencies": {
     "@types/node": "*",
+    "esbuild-register": ">=3.1.0",
     "ts-node": ">=9.0.0"
   },
   "peerDependenciesMeta": {
     "@types/node": {
       "optional": true
     },
+    "esbuild-register": {
+      "optional": true
+    },
     "ts-node": {
       "optional": true
     }
@@ -39,6 +43,7 @@
     "glob": "^7.1.3",
     "graceful-fs": "^4.2.9",
     "jest-circus": "workspace:^",
+    "jest-docblock": "workspace:^",
     "jest-environment-node": "workspace:^",
     "jest-get-type": "workspace:^",
     "jest-regex-util": "workspace:^",
@@ -57,6 +62,8 @@
     "@types/graceful-fs": "^4.1.3",
     "@types/micromatch": "^4.0.1",
     "@types/parse-json": "^4.0.0",
+    "esbuild": "^0.15.0",
+    "esbuild-register": "^3.1.0",
     "semver": "^7.3.5",
     "ts-node": "^10.5.0",
     "typescript": "^4.8.2"
diff --git a/packages/jest-config/src/readConfigFileAndSetRootDir.ts b/packages/jest-config/src/readConfigFileAndSetRootDir.ts
index a4496333ae32..948756ba52ed 100644
--- a/packages/jest-config/src/readConfigFileAndSetRootDir.ts
+++ b/packages/jest-config/src/readConfigFileAndSetRootDir.ts
@@ -9,8 +9,8 @@ import * as path from 'path';
 import * as fs from 'graceful-fs';
 import parseJson = require('parse-json');
 import stripJsonComments = require('strip-json-comments');
-import type {Service} from 'ts-node';
 import type {Config} from '@jest/types';
+import {extract, parse} from 'jest-docblock';
 import {interopRequireDefault, requireOrImportModule} from 'jest-util';
 import {
   JEST_CONFIG_EXT_JSON,
@@ -18,6 +18,12 @@ import {
   PACKAGE_JSON,
 } from './constants';
 
+interface TsLoader {
+  enabled: (bool: boolean) => void;
+}
+
+type TsLoaderModule = 'ts-node' | 'esbuild-register';
+
 // Read the configuration and set its `rootDir`
 // 1. If it's a `package.json` file, we look into its "jest" property
 // 2. If it's a `jest.config.ts` file, we use `ts-node` to transpile & require it
@@ -82,7 +88,19 @@ const loadTSConfigFile = async (
   configPath: string,
 ): Promise<Config.InitialOptions> => {
   // Get registered TypeScript compiler instance
-  const registeredCompiler = await getRegisteredCompiler();
+  const docblockPragmas = parse(extract(fs.readFileSync(configPath, 'utf8')));
+  const tsLoader = docblockPragmas['jest-config-loader'] || 'ts-node';
+  if (Array.isArray(tsLoader)) {
+    throw new Error(
+      `You can only define a single test environment through docblocks, got "${tsLoader.join(
+        ', ',
+      )}"`,
+    );
+  }
+
+  const registeredCompiler = await getRegisteredCompiler(
+    tsLoader as TsLoaderModule,
+  );
 
   registeredCompiler.enabled(true);
 
@@ -98,30 +116,50 @@ const loadTSConfigFile = async (
   return configObject;
 };
 
-let registeredCompilerPromise: Promise<Service>;
+let registeredCompilerPromise: Promise<TsLoader>;
 
-function getRegisteredCompiler() {
+function getRegisteredCompiler(loader: TsLoaderModule) {
   // Cache the promise to avoid multiple registrations
-  registeredCompilerPromise = registeredCompilerPromise ?? registerTsNode();
+  registeredCompilerPromise =
+    registeredCompilerPromise ?? registerTsLoader(loader);
   return registeredCompilerPromise;
 }
 
-async function registerTsNode(): Promise<Service> {
+async function registerTsLoader(loader: TsLoaderModule): Promise<TsLoader> {
   try {
     // Register TypeScript compiler instance
-    const tsNode = await import('ts-node');
-    return tsNode.register({
-      compilerOptions: {
-        module: 'CommonJS',
-      },
-      moduleTypes: {
-        '**': 'cjs',
-      },
-    });
+    if (loader === 'ts-node') {
+      const tsLoader = await import('ts-node');
+      return tsLoader.register({
+        compilerOptions: {
+          module: 'CommonJS',
+        },
+        moduleTypes: {
+          '**': 'cjs',
+        },
+      });
+    } else if (loader === 'esbuild-register') {
+      const tsLoader = await import('esbuild-register/dist/node');
+      let instance: {unregister: () => void} | undefined;
+      return {
+        enabled: (bool: boolean) => {
+          if (bool) {
+            instance = tsLoader.register({
+              target: `node${process.version.slice(1)}`,
+            });
+          } else {
+            instance?.unregister();
+          }
+        },
+      };
+    }
+    throw new Error(
+      `Jest: '${loader}' is not a valid TypeScript configuration loader.`,
+    );
   } catch (e: any) {
     if (e.code === 'ERR_MODULE_NOT_FOUND') {
       throw new Error(
-        `Jest: 'ts-node' is required for the TypeScript configuration files. Make sure it is installed\nError: ${e.message}`,
+        `Jest: '${loader}' is required for the TypeScript configuration files. Make sure it is installed\nError: ${e.message}`,
       );
     }
 
diff --git a/packages/jest-config/tsconfig.json b/packages/jest-config/tsconfig.json
index 6ed9554e6476..1f8bb9aed574 100644
--- a/packages/jest-config/tsconfig.json
+++ b/packages/jest-config/tsconfig.json
@@ -10,6 +10,7 @@
   // jest-test-sequencer, but that is just `require.resolve`d, so no real use
   // for their types
   "references": [
+    {"path": "../jest-docblock"},
     {"path": "../jest-environment-node"},
     {"path": "../jest-get-type"},
     {"path": "../jest-regex-util"},
diff --git a/yarn.lock b/yarn.lock
index 3b8fd2747236..3863ab7f0ee2 100644
--- a/yarn.lock
+++ b/yarn.lock
@@ -2496,6 +2496,20 @@ __metadata:
   languageName: node
   linkType: hard
 
+"@esbuild/android-arm@npm:0.15.18":
+  version: 0.15.18
+  resolution: "@esbuild/android-arm@npm:0.15.18"
+  conditions: os=android & cpu=arm
+  languageName: node
+  linkType: hard
+
+"@esbuild/linux-loong64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "@esbuild/linux-loong64@npm:0.15.18"
+  conditions: os=linux & cpu=loong64
+  languageName: node
+  linkType: hard
+
 "@eslint/eslintrc@npm:^1.4.1":
   version: 1.4.1
   resolution: "@eslint/eslintrc@npm:1.4.1"
@@ -9114,6 +9128,234 @@ __metadata:
   languageName: node
   linkType: hard
 
+"esbuild-android-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-android-64@npm:0.15.18"
+  conditions: os=android & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-android-arm64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-android-arm64@npm:0.15.18"
+  conditions: os=android & cpu=arm64
+  languageName: node
+  linkType: hard
+
+"esbuild-darwin-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-darwin-64@npm:0.15.18"
+  conditions: os=darwin & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-darwin-arm64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-darwin-arm64@npm:0.15.18"
+  conditions: os=darwin & cpu=arm64
+  languageName: node
+  linkType: hard
+
+"esbuild-freebsd-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-freebsd-64@npm:0.15.18"
+  conditions: os=freebsd & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-freebsd-arm64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-freebsd-arm64@npm:0.15.18"
+  conditions: os=freebsd & cpu=arm64
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-32@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-32@npm:0.15.18"
+  conditions: os=linux & cpu=ia32
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-64@npm:0.15.18"
+  conditions: os=linux & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-arm64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-arm64@npm:0.15.18"
+  conditions: os=linux & cpu=arm64
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-arm@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-arm@npm:0.15.18"
+  conditions: os=linux & cpu=arm
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-mips64le@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-mips64le@npm:0.15.18"
+  conditions: os=linux & cpu=mips64el
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-ppc64le@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-ppc64le@npm:0.15.18"
+  conditions: os=linux & cpu=ppc64
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-riscv64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-riscv64@npm:0.15.18"
+  conditions: os=linux & cpu=riscv64
+  languageName: node
+  linkType: hard
+
+"esbuild-linux-s390x@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-linux-s390x@npm:0.15.18"
+  conditions: os=linux & cpu=s390x
+  languageName: node
+  linkType: hard
+
+"esbuild-netbsd-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-netbsd-64@npm:0.15.18"
+  conditions: os=netbsd & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-openbsd-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-openbsd-64@npm:0.15.18"
+  conditions: os=openbsd & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-register@npm:^3.1.0":
+  version: 3.4.2
+  resolution: "esbuild-register@npm:3.4.2"
+  dependencies:
+    debug: ^4.3.4
+  peerDependencies:
+    esbuild: ">=0.12 <1"
+  checksum: f65d1ccb58b1ccbba376efb1fc023abe22731d9b79eead1b0120e57d4413318f063696257a5af637b527fa1d3f009095aa6edb1bf6ff69d637a9ab281fb727b3
+  languageName: node
+  linkType: hard
+
+"esbuild-sunos-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-sunos-64@npm:0.15.18"
+  conditions: os=sunos & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-windows-32@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-windows-32@npm:0.15.18"
+  conditions: os=win32 & cpu=ia32
+  languageName: node
+  linkType: hard
+
+"esbuild-windows-64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-windows-64@npm:0.15.18"
+  conditions: os=win32 & cpu=x64
+  languageName: node
+  linkType: hard
+
+"esbuild-windows-arm64@npm:0.15.18":
+  version: 0.15.18
+  resolution: "esbuild-windows-arm64@npm:0.15.18"
+  conditions: os=win32 & cpu=arm64
+  languageName: node
+  linkType: hard
+
+"esbuild@npm:^0.15.0":
+  version: 0.15.18
+  resolution: "esbuild@npm:0.15.18"
+  dependencies:
+    "@esbuild/android-arm": 0.15.18
+    "@esbuild/linux-loong64": 0.15.18
+    esbuild-android-64: 0.15.18
+    esbuild-android-arm64: 0.15.18
+    esbuild-darwin-64: 0.15.18
+    esbuild-darwin-arm64: 0.15.18
+    esbuild-freebsd-64: 0.15.18
+    esbuild-freebsd-arm64: 0.15.18
+    esbuild-linux-32: 0.15.18
+    esbuild-linux-64: 0.15.18
+    esbuild-linux-arm: 0.15.18
+    esbuild-linux-arm64: 0.15.18
+    esbuild-linux-mips64le: 0.15.18
+    esbuild-linux-ppc64le: 0.15.18
+    esbuild-linux-riscv64: 0.15.18
+    esbuild-linux-s390x: 0.15.18
+    esbuild-netbsd-64: 0.15.18
+    esbuild-openbsd-64: 0.15.18
+    esbuild-sunos-64: 0.15.18
+    esbuild-windows-32: 0.15.18
+    esbuild-windows-64: 0.15.18
+    esbuild-windows-arm64: 0.15.18
+  dependenciesMeta:
+    "@esbuild/android-arm":
+      optional: true
+    "@esbuild/linux-loong64":
+      optional: true
+    esbuild-android-64:
+      optional: true
+    esbuild-android-arm64:
+      optional: true
+    esbuild-darwin-64:
+      optional: true
+    esbuild-darwin-arm64:
+      optional: true
+    esbuild-freebsd-64:
+      optional: true
+    esbuild-freebsd-arm64:
+      optional: true
+    esbuild-linux-32:
+      optional: true
+    esbuild-linux-64:
+      optional: true
+    esbuild-linux-arm:
+      optional: true
+    esbuild-linux-arm64:
+      optional: true
+    esbuild-linux-mips64le:
+      optional: true
+    esbuild-linux-ppc64le:
+      optional: true
+    esbuild-linux-riscv64:
+      optional: true
+    esbuild-linux-s390x:
+      optional: true
+    esbuild-netbsd-64:
+      optional: true
+    esbuild-openbsd-64:
+      optional: true
+    esbuild-sunos-64:
+      optional: true
+    esbuild-windows-32:
+      optional: true
+    esbuild-windows-64:
+      optional: true
+    esbuild-windows-arm64:
+      optional: true
+  bin:
+    esbuild: bin/esbuild
+  checksum: ec12682b2cb2d4f0669d0e555028b87a9284ca7f6a1b26e35e69a8697165b35cc682ad598abc70f0bbcfdc12ca84ef888caf5ceee389237862e8f8c17da85f89
+  languageName: node
+  linkType: hard
+
 "escalade@npm:^3.1.1":
   version: 3.1.1
   resolution: "escalade@npm:3.1.1"
@@ -12580,9 +12822,12 @@ __metadata:
     chalk: ^4.0.0
     ci-info: ^3.2.0
     deepmerge: ^4.2.2
+    esbuild: ^0.15.0
+    esbuild-register: ^3.1.0
     glob: ^7.1.3
     graceful-fs: ^4.2.9
     jest-circus: "workspace:^"
+    jest-docblock: "workspace:^"
     jest-environment-node: "workspace:^"
     jest-get-type: "workspace:^"
     jest-regex-util: "workspace:^"
@@ -12600,10 +12845,13 @@ __metadata:
     typescript: ^4.8.2
   peerDependencies:
     "@types/node": "*"
+    esbuild-register: ">=3.1.0"
     ts-node: ">=9.0.0"
   peerDependenciesMeta:
     "@types/node":
       optional: true
+    esbuild-register:
+      optional: true
     ts-node:
       optional: true
   languageName: unknown