diff --git a/pkg/ccl/logictestccl/testdata/logic_test/multi_region b/pkg/ccl/logictestccl/testdata/logic_test/multi_region
index 068c8d5ab0e2..98b8905a6102 100644
--- a/pkg/ccl/logictestccl/testdata/logic_test/multi_region
+++ b/pkg/ccl/logictestccl/testdata/logic_test/multi_region
@@ -544,7 +544,7 @@ ALTER DATABASE system PRIMARY REGION "ap-southeast-2"
 # are in the system tenant. Hence the lack of error code checking and the
 # regex matching both possible outcomes.
 skipif config multiregion-9node-3region-3azs-tenant
-statement error user testuser may not modify the system database|modifying the regions of system database is not supported
+statement error user testuser may not modify the system database|Modifying the regions of system database is not supported. Set up your system database as multi-region using the cluster setting `sql.multiregion.preview_multiregion_system_database.enabled` https://www.cockroachlabs.com/docs/stable/cluster-settings
 ALTER DATABASE system PRIMARY REGION "ap-southeast-2"
 
 user root
diff --git a/pkg/ccl/multiregionccl/multiregion_system_table_test.go b/pkg/ccl/multiregionccl/multiregion_system_table_test.go
index 3776bb258910..b8b4249f5a15 100644
--- a/pkg/ccl/multiregionccl/multiregion_system_table_test.go
+++ b/pkg/ccl/multiregionccl/multiregion_system_table_test.go
@@ -48,7 +48,7 @@ func TestMrSystemDatabase(t *testing.T) {
 		return cs
 	}
 
-	cluster, _, cleanup := multiregionccltestutils.TestingCreateMultiRegionCluster(t, 3,
+	cluster, sqlDB, cleanup := multiregionccltestutils.TestingCreateMultiRegionCluster(t, 3,
 		base.TestingKnobs{},
 		multiregionccltestutils.WithSettings(makeSettings()))
 	defer cleanup()
@@ -81,6 +81,15 @@ func TestMrSystemDatabase(t *testing.T) {
 	// okay.
 	tDB.CheckQueryResults(t, `SELECT * FROM crdb_internal.invalid_objects`, [][]string{})
 
+	_, err = sqlDB.Exec(`SET CLUSTER SETTING sql.multiregion.preview_multiregion_system_database.enabled = true`)
+	require.NoError(t, err)
+	_, err = sqlDB.Exec(`ALTER DATABASE system SET PRIMARY REGION "us-east1"`)
+	require.NoError(t, err)
+	_, err = sqlDB.Exec(`ALTER DATABASE system ADD REGION "us-east2"`)
+	require.NoError(t, err)
+	_, err = sqlDB.Exec(`ALTER DATABASE system ADD REGION "us-east3"`)
+	require.NoError(t, err)
+
 	t.Run("Sqlliveness", func(t *testing.T) {
 		row := tDB.QueryRow(t, `SELECT crdb_region, session_id, expiration FROM system.sqlliveness LIMIT 1`)
 		var sessionID string
diff --git a/pkg/cmd/roachtest/tests/BUILD.bazel b/pkg/cmd/roachtest/tests/BUILD.bazel
index 190b9778eeba..67b0076cd548 100644
--- a/pkg/cmd/roachtest/tests/BUILD.bazel
+++ b/pkg/cmd/roachtest/tests/BUILD.bazel
@@ -113,6 +113,7 @@ go_library(
         "mixed_version_job_compatibility_in_declarative_schema_changer.go",
         "mixed_version_multi_region.go",
         "mixed_version_schemachange.go",
+        "multi_region_system_database.go",
         "multiregion_leasing.go",
         "multitenant.go",
         "multitenant_distsql.go",
diff --git a/pkg/cmd/roachtest/tests/multi_region_system_database.go b/pkg/cmd/roachtest/tests/multi_region_system_database.go
new file mode 100644
index 000000000000..1b3d8c70878b
--- /dev/null
+++ b/pkg/cmd/roachtest/tests/multi_region_system_database.go
@@ -0,0 +1,127 @@
+// Copyright 2024 The Cockroach Authors.
+//
+// Use of this software is governed by the Business Source License
+// included in the file licenses/BSL.txt.
+//
+// As of the Change Date specified in that file, in accordance with
+// the Business Source License, use of this software will be governed
+// by the Apache License, Version 2.0, included in the file
+// licenses/APL.txt.
+
+package tests
+
+import (
+	"context"
+	"fmt"
+	"strings"
+	"time"
+
+	"github.com/cockroachdb/cockroach/pkg/cmd/roachtest/cluster"
+	"github.com/cockroachdb/cockroach/pkg/cmd/roachtest/option"
+	"github.com/cockroachdb/cockroach/pkg/cmd/roachtest/registry"
+	"github.com/cockroachdb/cockroach/pkg/cmd/roachtest/spec"
+	"github.com/cockroachdb/cockroach/pkg/cmd/roachtest/test"
+	"github.com/cockroachdb/cockroach/pkg/roachprod/install"
+	"github.com/stretchr/testify/require"
+)
+
+func registerMultiRegionSystemDatabase(r registry.Registry) {
+	clusterSpec := r.MakeClusterSpec(3, spec.Geo(), spec.GatherCores(), spec.GCEZones("us-east1-b,us-west1-b,us-central1-b"))
+	r.Add(registry.TestSpec{
+		Name:             "multi-region-system-database",
+		Owner:            registry.OwnerSQLFoundations,
+		Timeout:          time.Hour * 1,
+		RequiresLicense:  true,
+		Cluster:          clusterSpec,
+		CompatibleClouds: registry.OnlyGCE,
+		Suites:           registry.Suites(registry.Weekly),
+		Run: func(ctx context.Context, t test.Test, c cluster.Cluster) {
+			nodes := c.Spec().NodeCount
+			regions := strings.Split(c.Spec().GCE.Zones, ",")
+			regionOnly := func(regionAndZone string) string {
+				r := strings.Split(regionAndZone, "-")
+				return r[0] + "-" + r[1]
+			}
+			t.Status("starting cluster")
+			c.Start(ctx, t.L(), option.DefaultStartOpts(), install.MakeClusterSettings(install.SecureOption(false)))
+			conn := c.Conn(ctx, t.L(), 1)
+			defer conn.Close()
+
+			_, err := conn.ExecContext(ctx, "SET CLUSTER SETTING sql.multiregion.preview_multiregion_system_database.enabled = true")
+			require.NoError(t, err)
+
+			_, err = conn.ExecContext(ctx,
+				fmt.Sprintf(`ALTER DATABASE system SET PRIMARY REGION '%s'`, regionOnly(regions[0])))
+			require.NoError(t, err)
+
+			_, err = conn.ExecContext(ctx,
+				fmt.Sprintf(`ALTER DATABASE system ADD REGION '%s'`, regionOnly(regions[1])))
+			require.NoError(t, err)
+
+			_, err = conn.ExecContext(ctx,
+				fmt.Sprintf(`ALTER DATABASE system ADD REGION '%s'`, regionOnly(regions[2])))
+			require.NoError(t, err)
+
+			//Perform rolling restart to propagate region information to non-primary nodes
+			for i := 2; i <= nodes; i++ {
+				t.WorkerStatus("stop")
+				err := c.StopCockroachGracefullyOnNode(ctx, t.L(), i)
+				if err != nil {
+					return
+				}
+				t.WorkerStatus("start")
+				startOpts := option.DefaultStartOpts()
+				c.Start(ctx, t.L(), startOpts, install.MakeClusterSettings(install.SecureOption(false)), c.Node(i))
+			}
+
+			//Check system.lease table to ensure that region information for each node is correct
+			rows, err := conn.Query("SELECT DISTINCT sql_instance_id, crdb_region FROM system.lease")
+			require.NoError(t, err)
+
+			nodeToRegionName := make(map[int]string)
+			for rows.Next() {
+				var sqlInstanceID int
+				var crdbRegion string
+				require.NoError(t, rows.Scan(&sqlInstanceID, &crdbRegion))
+				nodeToRegionName[sqlInstanceID] = crdbRegion
+			}
+
+			for node, regionName := range nodeToRegionName {
+				require.Equal(t, regionOnly(regions[node-1]), regionName)
+			}
+
+			//Intentionally tear down nodes and ensure that everything is still working
+			chaosTest := func() {
+				//Random operations on user-created table
+				_, err := conn.Exec(`CREATE TABLE foo (key INT PRIMARY KEY)`)
+				if err != nil {
+					return
+				}
+				defer func() {
+					_, err := conn.Exec(`DROP TABLE foo`)
+					if err != nil {
+						return
+					}
+				}()
+				_, err = conn.Exec(`INSERT INTO foo VALUES (1), (2), (3)`)
+				require.NoError(t, err)
+				row := conn.QueryRow(`SELECT * FROM foo LIMIT 1`)
+				var rowPK int
+				require.NoError(t, row.Scan(&rowPK))
+				require.Equal(t, 1, rowPK)
+			}
+
+			for i := 2; i <= nodes; i++ {
+				t.WorkerStatus("stop")
+				c.Run(ctx, option.WithNodes(c.Node(i)), "killall -9 cockroach")
+
+				t.WorkerStatus("chaos testing")
+				chaosTest()
+
+				t.WorkerStatus("start")
+				startOpts := option.DefaultStartOpts()
+				c.Start(ctx, t.L(), startOpts, install.MakeClusterSettings(install.SecureOption(false)), c.Node(i))
+			}
+		},
+	})
+}
diff --git a/pkg/cmd/roachtest/tests/registry.go b/pkg/cmd/roachtest/tests/registry.go
index be40147c0f9e..f785131507b3 100644
--- a/pkg/cmd/roachtest/tests/registry.go
+++ b/pkg/cmd/roachtest/tests/registry.go
@@ -154,4 +154,5 @@ func RegisterTests(r registry.Registry) {
 	registerYCSB(r)
 	registerDeclarativeSchemaChangerJobCompatibilityInMixedVersion(r)
 	registerMultiRegionMixedVersion(r)
+	registerMultiRegionSystemDatabase(r)
 }
diff --git a/pkg/sql/alter_database.go b/pkg/sql/alter_database.go
index 07348685b54e..ae0bef4bf727 100644
--- a/pkg/sql/alter_database.go
+++ b/pkg/sql/alter_database.go
@@ -269,6 +269,11 @@ func (n *alterDatabaseAddRegionNode) startExec(params runParams) error {
 		if err := params.p.setSystemDatabaseSurvival(params.ctx); err != nil {
 			return err
 		}
+
+		params.p.BufferClientNotice(
+			params.ctx,
+			pgnotice.Newf("Rolling restart is recommended after adding a region to system database in order to propogate region information."),
+		)
 	}
 
 	// Validate the type descriptor after the changes. We have to do this explicitly here, because
@@ -586,10 +591,14 @@ func (p *planner) checkPrivilegesForMultiRegionOp(
 	// multi-region primitives in the system database. For now, we also allow
 	// root to perform the various operations to enable testing.
 	if desc.GetID() == keys.SystemDatabaseID {
-		if p.execCfg.Codec.ForSystemTenant() {
+		if multiRegionSystemDatabase := sqlclustersettings.MultiRegionSystemDatabaseEnabled.Get(&p.execCfg.Settings.SV); !multiRegionSystemDatabase &&
+			p.execCfg.Codec.ForSystemTenant() {
 			return pgerror.Newf(
 				pgcode.FeatureNotSupported,
-				"modifying the regions of system database is not supported",
+				"Modifying the regions of system database is not supported. "+
+					"Set up your system database as multi-region using the cluster setting "+
+					"`sql.multiregion.preview_multiregion_system_database.enabled` "+
+					"https://www.cockroachlabs.com/docs/stable/cluster-settings.",
 			)
 		}
 		if u := p.SessionData().User(); !u.IsNodeUser() && !u.IsRootUser() {
diff --git a/pkg/sql/sqlclustersettings/clustersettings.go b/pkg/sql/sqlclustersettings/clustersettings.go
index b96a3df09736..e51c2413c48b 100644
--- a/pkg/sql/sqlclustersettings/clustersettings.go
+++ b/pkg/sql/sqlclustersettings/clustersettings.go
@@ -79,6 +79,15 @@ var SecondaryTenantsAllZoneConfigsEnabled = settings.RegisterBoolSetting(
 	true,
 )
 
+// MultiRegionSystemDatabaseEnabled controls if system tenants are allowed
+// to be set up to be multi-region.
+var MultiRegionSystemDatabaseEnabled = settings.RegisterBoolSetting(
+	settings.SystemVisible,
+	"sql.multiregion.preview_multiregion_system_database.enabled",
+	"enable option to set up system database as multi-region",
+	false,
+)
+
 // RequireSystemTenantOrClusterSetting returns a setting disabled error if
 // executed from inside a secondary tenant that does not have the specified
 // cluster setting.