diff --git a/base/initdefs.jl b/base/initdefs.jl
index 4106ef4eb7777..f7a02291a8840 100644
--- a/base/initdefs.jl
+++ b/base/initdefs.jl
@@ -350,6 +350,7 @@ end
 const atexit_hooks = Callable[
     () -> Filesystem.temp_cleanup_purge(force=true)
 ]
+const _atexit_hooks_lock = ReentrantLock()
 
 """
     atexit(f)
@@ -363,7 +364,7 @@ calls `exit(n)`, then Julia will exit with the exit code corresponding to the
 last called exit hook that calls `exit(n)`. (Because exit hooks are called in
 LIFO order, "last called" is equivalent to "first registered".)
 """
-atexit(f::Function) = (pushfirst!(atexit_hooks, f); nothing)
+atexit(f::Function) = Base.@lock _atexit_hooks_lock (pushfirst!(atexit_hooks, f); nothing)
 
 function _atexit()
     while !isempty(atexit_hooks)
diff --git a/test/threads_exec.jl b/test/threads_exec.jl
index 9cd5992d90a74..52e45fa381ec2 100644
--- a/test/threads_exec.jl
+++ b/test/threads_exec.jl
@@ -1062,3 +1062,24 @@ end
         popfirst!(LOAD_PATH)
     end
 end
+
+# issue #49746, thread safety in `atexit(f)`
+@testset "atexit thread safety" begin
+    f = () -> nothing
+    before_len = length(Base.atexit_hooks)
+    @sync begin
+        for _ in 1:1_000_000
+            Threads.@spawn begin
+                atexit(f)
+            end
+        end
+    end
+    @test length(Base.atexit_hooks) == before_len + 1_000_000
+    @test all(hook -> hook === f, Base.atexit_hooks[1 : 1_000_000])
+
+    # cleanup
+    Base.@lock Base._atexit_hooks_lock begin
+        deleteat!(Base.atexit_hooks, 1:1_000_000)
+    end
+end
+