diff --git a/doc/api/tls.md b/doc/api/tls.md
index 7e443fb66e5021..40736aef4b1b7a 100644
--- a/doc/api/tls.md
+++ b/doc/api/tls.md
@@ -2260,6 +2260,25 @@ openssl pkcs12 -certpbe AES-256-CBC -export -out client-cert.pem \
 The server can be tested by connecting to it using the example client from
 [`tls.connect()`][].
 
+## `tls.useSystemCA()`
+
+<!-- YAML
+added: REPLACEME
+-->
+
+Enables system CA certificates to be used by the Node.js TLS clients by default.
+This is equivalent to enabling the [`--use-system-ca`][] flag, but can be done
+programmatically at runtime.
+
+Once called, the system CA certificates will be included in the default CA
+certificate list returned by [`tls.getCACertificates()`][] and used by TLS
+connections that don't specify their own CA certificates.
+
+Subsequent calls to this function are no-ops. The system CA certificates are
+loaded and cached on the first call.
+
+This function only affects the current Node.js thread.
+
 ## `tls.getCACertificates([type])`
 
 <!-- YAML
diff --git a/lib/tls.js b/lib/tls.js
index 88793f19ef7698..4d482d361bb50a 100644
--- a/lib/tls.js
+++ b/lib/tls.js
@@ -51,6 +51,7 @@ const {
   getBundledRootCertificates,
   getExtraCACertificates,
   getSystemCACertificates,
+  useSystemCA: useSystemCABinding,
   getSSLCiphers,
 } = internalBinding('crypto');
 const { Buffer } = require('buffer');
@@ -122,6 +123,21 @@ function cacheSystemCACertificates() {
 }
 
 let defaultCACertificates;
+let enabledSystemCACertificates = false;
+function useSystemCA() {
+  if (enabledSystemCACertificates) {
+    // Already enabled. It's a no-op.
+    return;
+  }
+
+  useSystemCABinding();
+  enabledSystemCACertificates = true;
+  // Invalidate the cached values so that they will be
+  // recalculated the next time tls.getCACertificates() is called.
+  systemCACertificates = undefined;
+  defaultCACertificates = undefined;
+}
+
 function cacheDefaultCACertificates() {
   if (defaultCACertificates) { return defaultCACertificates; }
   defaultCACertificates = [];
@@ -131,7 +147,7 @@ function cacheDefaultCACertificates() {
     for (let i = 0; i < bundled.length; ++i) {
       ArrayPrototypePush(defaultCACertificates, bundled[i]);
     }
-    if (getOptionValue('--use-system-ca')) {
+    if (getOptionValue('--use-system-ca') || enabledSystemCACertificates) {
       const system = cacheSystemCACertificates();
       for (let i = 0; i < system.length; ++i) {
 
@@ -170,6 +186,7 @@ function getCACertificates(type = 'default') {
   }
 }
 exports.getCACertificates = getCACertificates;
+exports.useSystemCA = useSystemCA;
 
 // Convert protocols array into valid OpenSSL protocols list
 // ("\x06spdy/2\x08http/1.1\x08http/1.0")
diff --git a/src/crypto/crypto_context.cc b/src/crypto/crypto_context.cc
index 1ffce89df5f760..cf2b13a7201948 100644
--- a/src/crypto/crypto_context.cc
+++ b/src/crypto/crypto_context.cc
@@ -84,11 +84,15 @@ static std::string extra_root_certs_file;  // NOLINT(runtime/string)
 static std::atomic<bool> has_cached_bundled_root_certs{false};
 static std::atomic<bool> has_cached_system_root_certs{false};
 static std::atomic<bool> has_cached_extra_root_certs{false};
-
+// Per-thread root cert store.
+static thread_local X509_STORE* root_cert_store = nullptr;
+static bool use_system_ca_in_root_cert_store = false;
 X509_STORE* GetOrCreateRootCertStore() {
-  // Guaranteed thread-safe by standard, just don't use -fno-threadsafe-statics.
-  static X509_STORE* store = NewRootCertStore();
-  return store;
+  if (root_cert_store != nullptr) {
+    return root_cert_store;
+  }
+  root_cert_store = NewRootCertStore();
+  return root_cert_store;
 }
 
 // Takes a string or buffer and loads it into a BIO.
@@ -851,7 +855,8 @@ X509_STORE* NewRootCertStore() {
     for (X509* cert : GetBundledRootCertificates()) {
       CHECK_EQ(1, X509_STORE_add_cert(store, cert));
     }
-    if (per_process::cli_options->use_system_ca) {
+    if (per_process::cli_options->use_system_ca ||
+        use_system_ca_in_root_cert_store) {
       for (X509* cert : GetSystemStoreCACertificates()) {
         CHECK_EQ(1, X509_STORE_add_cert(store, cert));
       }
@@ -935,6 +940,17 @@ MaybeLocal<Array> X509sToArrayOfStrings(Environment* env,
   return scope.Escape(Array::New(env->isolate(), result.data(), result.size()));
 }
 
+void UseSystemCA(const FunctionCallbackInfo<Value>& args) {
+  Environment* env = Environment::GetCurrent(args);
+  use_system_ca_in_root_cert_store = true;
+  X509_STORE* store = GetOrCreateRootCertStore();
+  for (X509* cert : GetSystemStoreCACertificates()) {
+    if (!X509_STORE_add_cert(store, cert)) {
+      return ThrowCryptoError(env, ERR_get_error(), "X509_STORE_add_cert");
+    }
+  }
+}
+
 void GetSystemCACertificates(const FunctionCallbackInfo<Value>& args) {
   Environment* env = Environment::GetCurrent(args);
   Local<Array> results;
@@ -1046,6 +1062,7 @@ void SecureContext::Initialize(Environment* env, Local<Object> target) {
       context, target, "getSystemCACertificates", GetSystemCACertificates);
   SetMethodNoSideEffect(
       context, target, "getExtraCACertificates", GetExtraCACertificates);
+  SetMethodNoSideEffect(context, target, "useSystemCA", UseSystemCA);
 }
 
 void SecureContext::RegisterExternalReferences(
@@ -1088,6 +1105,7 @@ void SecureContext::RegisterExternalReferences(
   registry->Register(GetBundledRootCertificates);
   registry->Register(GetSystemCACertificates);
   registry->Register(GetExtraCACertificates);
+  registry->Register(UseSystemCA);
 }
 
 SecureContext* SecureContext::Create(Environment* env) {
diff --git a/test/parallel/test-tls-use-system-ca-certificates-with-flag.js b/test/parallel/test-tls-use-system-ca-certificates-with-flag.js
new file mode 100644
index 00000000000000..ae7e9a84e9087c
--- /dev/null
+++ b/test/parallel/test-tls-use-system-ca-certificates-with-flag.js
@@ -0,0 +1,39 @@
+'use strict';
+// Flags: --use-system-ca
+
+// This tests that tls.useSystemCA() is a no-op when
+// --use-system-ca flag is already set.
+
+const common = require('../common');
+if (!common.hasCrypto) common.skip('missing crypto');
+
+const assert = require('assert');
+const tls = require('tls');
+
+// Get initial state when --use-system-ca is already set
+const initialDefaultCerts = tls.getCACertificates('default');
+const systemCerts = tls.getCACertificates('system');
+
+assert(Array.isArray(systemCerts));
+
+// With --use-system-ca, default should already include system certs
+const initialSystemSet = new Set(systemCerts);
+const initialDefaultSet = new Set(initialDefaultCerts);
+assert.deepStrictEqual(initialDefaultSet.intersection(initialSystemSet), initialSystemSet);
+
+// Enable system CA certificates (should be a no-op)
+tls.useSystemCA();
+
+// Get certificates after calling useSystemCA
+const newDefaultCerts = tls.getCACertificates('default');
+const newSystemCerts = tls.getCACertificates('system');
+
+// Everything should have the same content.
+assert.deepStrictEqual(initialDefaultCerts, newDefaultCerts);
+assert.deepStrictEqual(systemCerts, newSystemCerts);
+
+// Multiple calls should still be no-ops
+tls.useSystemCA();
+tls.useSystemCA();
+const stillSameDefaultCerts = tls.getCACertificates('default');
+assert.deepStrictEqual(newDefaultCerts, stillSameDefaultCerts);
diff --git a/test/parallel/test-tls-use-system-ca-certificates.js b/test/parallel/test-tls-use-system-ca-certificates.js
new file mode 100644
index 00000000000000..cb008c3aca4548
--- /dev/null
+++ b/test/parallel/test-tls-use-system-ca-certificates.js
@@ -0,0 +1,54 @@
+'use strict';
+
+// Flags: --no-use-system-ca
+// This tests that tls.useSystemCA() works correctly.
+
+const common = require('../common');
+if (!common.hasCrypto) common.skip('missing crypto');
+
+const assert = require('assert');
+const tls = require('tls');
+
+// Get initial state
+const initialDefaultCerts = tls.getCACertificates('default');
+const systemCerts = tls.getCACertificates('system');
+
+assert(Array.isArray(systemCerts));
+
+// Check that system certs are not included by default (without --use-system-ca)
+const initialSystemSet = new Set(systemCerts);
+const initialDefaultSet = new Set(initialDefaultCerts);
+const initialIntersection = initialDefaultSet.intersection(initialSystemSet);
+
+// The initial default should not contain all system certs
+// if there are system certs installed.
+if (systemCerts.length > 0) {
+  assert(initialIntersection.size < systemCerts.length);
+}
+
+// Enable system CA certificates.
+tls.useSystemCA();
+
+// Get certificates after enabling system CAs
+const newDefaultCerts = tls.getCACertificates('default');
+const newSystemCerts = tls.getCACertificates('system');
+
+// System certificates should have the same content
+assert.deepStrictEqual(systemCerts, newSystemCerts);
+
+// Default certificates behavior depends on whether system certs exist
+if (systemCerts.length > 0) {
+  // The new default should be old default plus system certs
+  const newDefaultSet = new Set(newDefaultCerts);
+  const newSystemSet = new Set(systemCerts);
+  assert.deepStrictEqual(newDefaultSet.intersection(initialDefaultSet), initialDefaultSet);
+  assert.deepStrictEqual(newDefaultSet.intersection(newSystemSet), newSystemSet);
+} else {
+  // If no system certs, default certs should remain the same
+  assert.deepStrictEqual(initialDefaultCerts, newDefaultCerts);
+}
+
+// Calling useSystemCA again should be a no-op
+tls.useSystemCA();
+const sameDefaultCerts = tls.getCACertificates('default');
+assert.deepStrictEqual(newDefaultCerts, sameDefaultCerts);
diff --git a/test/system-ca/test-use-system-ca-certificates.js b/test/system-ca/test-use-system-ca-certificates.js
new file mode 100644
index 00000000000000..2b13f0fdeec861
--- /dev/null
+++ b/test/system-ca/test-use-system-ca-certificates.js
@@ -0,0 +1,64 @@
+'use strict';
+
+// Flags: --no-use-system-ca
+
+// This tests that tls.useSystemCA() works correctly
+// when the certificates from the README are installed on the system.
+// To run this test, install the certificates as described in README.md
+
+const common = require('../common');
+if (!common.hasCrypto) common.skip('missing crypto');
+
+const assert = require('assert');
+const tls = require('tls');
+const { assertIsCAArray } = require('../common/tls');
+const fixtures = require('../common/fixtures');
+
+// Read the expected certificates that should be installed
+const startcomRootCert = fixtures.readKey('fake-startcom-root-cert.pem', 'utf8');
+
+// Get initial state.
+const initialDefaultCerts = tls.getCACertificates('default');
+const systemCerts = tls.getCACertificates('system');
+
+// System certs should be a valid CA array and should contain our test certificates
+assertIsCAArray(systemCerts);
+assert(systemCerts.length > 0, 'System certificates should be available when test certs are installed');
+
+assert(systemCerts.includes(startcomRootCert));
+assert(!initialDefaultCerts.includes(startcomRootCert));
+
+// Check that system certs are not included by default (without --use-system-ca)
+const initialSystemSet = new Set(systemCerts);
+const initialDefaultSet = new Set(initialDefaultCerts);
+const initialIntersection = initialDefaultSet.intersection(initialSystemSet);
+
+// The initial default should not contain all system certs
+assert(initialIntersection.size < systemCerts.length, 'Default certs should not include all system certs initially');
+
+// Enable system CA certificates
+tls.useSystemCA();
+
+// Get certificates after enabling system CAs
+const newDefaultCerts = tls.getCACertificates('default');
+const newSystemCerts = tls.getCACertificates('system');
+
+// System certificates should have the same content
+assert.deepStrictEqual(systemCerts, newSystemCerts);
+
+// Default certificates should now include the system certificates
+assert.notStrictEqual(initialDefaultCerts, newDefaultCerts, 'Default certs should change after enabling system CAs');
+
+// The new default should be a superset of system certificates
+assert(newDefaultCerts.length >= systemCerts.length, 'New default should include all system certs');
+const newDefaultSet = new Set(newDefaultCerts);
+const newSystemSet = new Set(systemCerts);
+assert.deepStrictEqual(newDefaultSet.intersection(newSystemSet), newSystemSet);
+
+// Verify that our test certificates are now in the default certs
+assert(newDefaultCerts.includes(startcomRootCert));
+
+// Calling useSystemCA again should be a no-op
+tls.useSystemCA();
+const sameDefaultCerts = tls.getCACertificates('default');
+assert.deepStrictEqual(newDefaultCerts, sameDefaultCerts);
diff --git a/test/system-ca/test-use-system-ca-dynamic.mjs b/test/system-ca/test-use-system-ca-dynamic.mjs
new file mode 100644
index 00000000000000..0aebe282d3b62a
--- /dev/null
+++ b/test/system-ca/test-use-system-ca-dynamic.mjs
@@ -0,0 +1,74 @@
+// Flags: --no-use-system-ca
+
+// This tests that tls.useSystemCA() dynamically enables
+// system certificates, allowing connections that would otherwise fail.
+// To run this test, install the certificates as described in README.md
+
+import * as common from '../common/index.mjs';
+import assert from 'node:assert/strict';
+import https from 'node:https';
+import tls from 'node:tls';
+import fixtures from '../common/fixtures.js';
+import { it, beforeEach, afterEach, describe } from 'node:test';
+import { once } from 'events';
+
+if (!common.hasCrypto) {
+  common.skip('requires crypto');
+}
+
+const handleRequest = (req, res) => {
+  const path = req.url;
+  switch (path) {
+    case '/hello-world':
+      res.writeHead(200);
+      res.end('hello world\n');
+      break;
+    default:
+      assert(false, `Unexpected path: ${path}`);
+  }
+};
+
+describe('enable-system-ca-dynamic', function() {
+  async function setupServer(key, cert) {
+    const theServer = https.createServer({
+      key: fixtures.readKey(key),
+      cert: fixtures.readKey(cert),
+    }, handleRequest);
+    theServer.listen(0);
+    await once(theServer, 'listening');
+
+    return theServer;
+  }
+
+  let server;
+
+  beforeEach(async function() {
+    server = await setupServer('agent8-key.pem', 'agent8-cert.pem');
+  });
+
+  it('fails before enabling system CA, succeeds after', async function() {
+    const url = `https://localhost:${server.address().port}/hello-world`;
+
+    // First attempt should fail without system certificates.
+    await assert.rejects(
+      fetch(url),
+      (err) => {
+        assert.strictEqual(err.cause.code, 'UNABLE_TO_VERIFY_LEAF_SIGNATURE');
+        return true;
+      },
+    );
+
+    // Now enable system CA certificates
+    tls.useSystemCA();
+
+    // Second attempt should succeed.
+    const response = await fetch(url);
+    assert.strictEqual(response.status, 200);
+    const text = await response.text();
+    assert.strictEqual(text, 'hello world\n');
+  });
+
+  afterEach(async function() {
+    server?.close();
+  });
+});