diff --git chrome/app/chrome_main_delegate.cc chrome/app/chrome_main_delegate.cc
index 495893eec9704..e967494683f19 100644
--- chrome/app/chrome_main_delegate.cc
+++ chrome/app/chrome_main_delegate.cc
@@ -29,6 +29,7 @@
 #include "base/trace_event/trace_event_impl.h"
 #include "build/build_config.h"
 #include "build/chromeos_buildflags.h"
+#include "cef/libcef/features/runtime.h"
 #include "chrome/browser/chrome_content_browser_client.h"
 #include "chrome/browser/chrome_resource_bundle_helper.h"
 #include "chrome/browser/defaults.h"
@@ -384,6 +385,8 @@ struct MainFunction {
 
 // Initializes the user data dir. Must be called before InitializeLocalState().
 void InitializeUserDataDir(base::CommandLine* command_line) {
+  if (cef::IsChromeRuntimeEnabled())
+    return;
 #if defined(OS_WIN)
   // Reach out to chrome_elf for the truth on the user data directory.
   // Note that in tests, this links to chrome_elf_test_stubs.
@@ -675,7 +678,9 @@ void ChromeMainDelegate::PostFieldTrialInitialization() {
   }
 
 #if defined(OS_WIN)
+  if (!cef::IsChromeRuntimeEnabled()) {
   SetUpExtendedCrashReporting(is_browser_process);
+  }
   base::sequence_manager::internal::ThreadControllerPowerMonitor::
       InitializeOnMainThread();
 #endif
@@ -970,6 +975,7 @@ void ChromeMainDelegate::PreSandboxStartup() {
   std::string process_type =
       command_line.GetSwitchValueASCII(switches::kProcessType);
 
+  if (!cef::IsChromeRuntimeEnabled()) {
   crash_reporter::InitializeCrashKeys();
 
 #if defined(OS_POSIX)
@@ -980,6 +986,7 @@ void ChromeMainDelegate::PreSandboxStartup() {
   InitMacCrashReporter(command_line, process_type);
   SetUpInstallerPreferences(command_line);
 #endif
+  }  // !cef::IsChromeRuntimeEnabled()
 
 #if defined(OS_WIN)
   child_process_logging::Init();
@@ -1103,6 +1110,7 @@ void ChromeMainDelegate::PreSandboxStartup() {
         locale;
   }
 
+  if (!cef::IsChromeRuntimeEnabled()) {
 #if defined(OS_POSIX) && !defined(OS_MAC)
   // Zygote needs to call InitCrashReporter() in RunZygote().
   if (process_type != switches::kZygoteProcess) {
@@ -1135,6 +1143,7 @@ void ChromeMainDelegate::PreSandboxStartup() {
   // After all the platform Breakpads have been initialized, store the command
   // line for crash reporting.
   crash_keys::SetCrashKeysFromCommandLine(command_line);
+  }  // !cef::IsChromeRuntimeEnabled()
 
 #if BUILDFLAG(ENABLE_PDF)
   MaybeInitializeGDI();
@@ -1233,6 +1242,7 @@ void ChromeMainDelegate::ZygoteForked() {
     SetUpProfilingShutdownHandler();
   }
 
+  if (!cef::IsChromeRuntimeEnabled()) {
   // Needs to be called after we have chrome::DIR_USER_DATA.  BrowserMain sets
   // this up for the browser process in a different manner.
   const base::CommandLine* command_line =
@@ -1249,6 +1259,7 @@ void ChromeMainDelegate::ZygoteForked() {
 
   // Reset the command line for the newly spawned process.
   crash_keys::SetCrashKeysFromCommandLine(*command_line);
+  }  // !cef::IsChromeRuntimeEnabled()
 }
 
 #endif  // defined(OS_LINUX) || defined(OS_CHROMEOS)
diff --git chrome/browser/chrome_browser_main.cc chrome/browser/chrome_browser_main.cc
index dff0a32062f0e..9378b2a0be47f 100644
--- chrome/browser/chrome_browser_main.cc
+++ chrome/browser/chrome_browser_main.cc
@@ -49,6 +49,7 @@
 #include "build/build_config.h"
 #include "build/chromeos_buildflags.h"
 #include "cc/base/switches.h"
+#include "cef/libcef/features/runtime.h"
 #include "chrome/browser/about_flags.h"
 #include "chrome/browser/active_use_util.h"
 #include "chrome/browser/after_startup_task_utils.h"
@@ -915,8 +916,10 @@ int ChromeBrowserMainParts::PreCreateThreadsImpl() {
 #if !defined(OS_ANDROID)
   // Create the RunLoop for MainMessageLoopRun() to use, and pass a copy of
   // its QuitClosure to the BrowserProcessImpl to call when it is time to exit.
+  // CEF with the Chrome runtime will create and manage its own RunLoop.
   DCHECK(!GetMainRunLoopInstance());
-  GetMainRunLoopInstance() = std::make_unique<base::RunLoop>();
+  if (!cef::IsChromeRuntimeEnabled())
+    GetMainRunLoopInstance() = std::make_unique<base::RunLoop>();
 
   // These members must be initialized before returning from this function.
   // Android doesn't use StartupBrowserCreator.
@@ -1689,11 +1692,14 @@ int ChromeBrowserMainParts::PreMainMessageLoopRunImpl() {
   // This step is costly and is already measured in
   // Startup.StartupBrowserCreator_Start.
   // See the comment above for an explanation of |process_command_line|.
+  // Bypass StartupBrowserCreator with CEF where |GetMainRunLoopInstance()| is
+  // nullptr.
   const bool started =
+      !GetMainRunLoopInstance() ||
       !process_command_line ||
       browser_creator_->Start(parsed_command_line(), base::FilePath(), profile_,
                               last_opened_profiles);
-  if (started) {
+  if (started && GetMainRunLoopInstance()) {
 // TODO(crbug.com/1052397): Revisit the macro expression once build flag switch
 // of lacros-chrome is complete.
 #if defined(OS_WIN) || (defined(OS_LINUX) || BUILDFLAG(IS_CHROMEOS_LACROS))
diff --git chrome/browser/chrome_browser_main_mac.mm chrome/browser/chrome_browser_main_mac.mm
index 95d1ebc190910..13cdfa52db108 100644
--- chrome/browser/chrome_browser_main_mac.mm
+++ chrome/browser/chrome_browser_main_mac.mm
@@ -16,6 +16,7 @@
 #include "base/path_service.h"
 #include "base/strings/sys_string_conversions.h"
 #include "build/branding_buildflags.h"
+#include "cef/libcef/features/features.h"
 #import "chrome/browser/app_controller_mac.h"
 #include "chrome/browser/apps/app_shim/app_shim_listener.h"
 #include "chrome/browser/browser_process.h"
@@ -110,6 +111,7 @@ void ChromeBrowserMainPartsMac::PreCreateMainMessageLoop() {
     }
   }
 
+#if !BUILDFLAG(ENABLE_CEF)
   // Create the app delegate. This object is intentionally leaked as a global
   // singleton. It is accessed through -[NSApp delegate].
   AppController* app_controller = [[AppController alloc] init];
@@ -118,6 +120,7 @@ void ChromeBrowserMainPartsMac::PreCreateMainMessageLoop() {
   chrome::BuildMainMenu(NSApp, app_controller,
                         l10n_util::GetStringUTF16(IDS_PRODUCT_NAME), false);
   [app_controller mainMenuCreated];
+#endif  // BUILDFLAG(ENABLE_CEF)
 
   PrefService* local_state = g_browser_process->local_state();
   DCHECK(local_state);
@@ -170,7 +173,9 @@ void ChromeBrowserMainPartsMac::PostProfileInit() {
 }
 
 void ChromeBrowserMainPartsMac::DidEndMainMessageLoop() {
+#if !BUILDFLAG(ENABLE_CEF)
   AppController* appController =
       base::mac::ObjCCastStrict<AppController>([NSApp delegate]);
   [appController didEndMainMessageLoop];
+#endif
 }
diff --git chrome/browser/chrome_content_browser_client.cc chrome/browser/chrome_content_browser_client.cc
index 8650dd04f9c44..45ab4913bbe04 100644
--- chrome/browser/chrome_content_browser_client.cc
+++ chrome/browser/chrome_content_browser_client.cc
@@ -38,6 +38,7 @@
 #include "base/threading/thread_task_runner_handle.h"
 #include "build/build_config.h"
 #include "build/chromeos_buildflags.h"
+#include "cef/libcef/features/features.h"
 #include "chrome/browser/accessibility/accessibility_labels_service.h"
 #include "chrome/browser/accessibility/accessibility_labels_service_factory.h"
 #include "chrome/browser/after_startup_task_utils.h"
@@ -3562,9 +3563,11 @@ void ChromeContentBrowserClient::BrowserURLHandlerCreated(
                           &search::HandleNewTabURLReverseRewrite);
 #endif  // defined(OS_ANDROID)
 
+#if !BUILDFLAG(ENABLE_CEF)
   // chrome: & friends.
   handler->AddHandlerPair(&ChromeContentBrowserClient::HandleWebUI,
                           &ChromeContentBrowserClient::HandleWebUIReverse);
+#endif
 }
 
 base::FilePath ChromeContentBrowserClient::GetDefaultDownloadDirectory() {
diff --git chrome/browser/notifications/alert_dispatcher_xpc.mm chrome/browser/notifications/alert_dispatcher_xpc.mm
index ab4c2b03755d3..8e813496f9df6 100644
--- chrome/browser/notifications/alert_dispatcher_xpc.mm
+++ chrome/browser/notifications/alert_dispatcher_xpc.mm
@@ -19,6 +19,7 @@
 #include "base/mac/scoped_nsobject.h"
 #include "base/metrics/histogram_functions.h"
 #include "base/strings/sys_string_conversions.h"
+#include "cef/libcef/features/runtime.h"
 #include "chrome/browser/notifications/notification_platform_bridge_mac_utils.h"
 #import "chrome/browser/ui/cocoa/notifications/notification_delivery.h"
 #include "chrome/browser/ui/cocoa/notifications/xpc_mach_port.h"
@@ -179,6 +180,12 @@ void RecordXPCEvent(XPCConnectionEvent event) {
 - (id<NotificationDelivery>)serviceProxy {
   id<NotificationDelivery> proxy = [_xpcConnection remoteObjectProxy];
 
+  // Skip exception port configuration when running CEF with crash reporting disabled.
+  if (!_setExceptionPort && cef::IsChromeRuntimeEnabled() &&
+      !cef::IsCrashReportingEnabled()) {
+    _setExceptionPort = YES;
+  }
+
   if (!_setExceptionPort) {
     base::mac::ScopedMachSendRight exceptionPort(
         crash_reporter::GetCrashpadClient().GetHandlerMachPort());
diff --git chrome/browser/prefs/browser_prefs.cc chrome/browser/prefs/browser_prefs.cc
index 3de6df64935e3..78a2bf3896e72 100644
--- chrome/browser/prefs/browser_prefs.cc
+++ chrome/browser/prefs/browser_prefs.cc
@@ -10,6 +10,7 @@
 #include "build/branding_buildflags.h"
 #include "build/build_config.h"
 #include "build/chromeos_buildflags.h"
+#include "cef/libcef/features/features.h"
 #include "chrome/browser/about_flags.h"
 #include "chrome/browser/accessibility/accessibility_labels_service.h"
 #include "chrome/browser/accessibility/accessibility_ui.h"
@@ -164,6 +165,10 @@
 #include "chrome/browser/background/background_mode_manager.h"
 #endif
 
+#if BUILDFLAG(ENABLE_CEF)
+#include "cef/libcef/browser/prefs/browser_prefs.h"
+#endif
+
 #if BUILDFLAG(ENABLE_EXTENSIONS)
 #include "chrome/browser/accessibility/animation_policy_prefs.h"
 #include "chrome/browser/apps/platform_apps/shortcut_manager.h"
@@ -1134,6 +1139,10 @@ void RegisterProfilePrefs(user_prefs::PrefRegistrySyncable* registry,
   SessionDataService::RegisterProfilePrefs(registry);
 #endif
 
+#if BUILDFLAG(ENABLE_CEF)
+  browser_prefs::RegisterProfilePrefs(registry);
+#endif
+
 #if BUILDFLAG(ENABLE_EXTENSIONS)
   ExtensionWebUI::RegisterProfilePrefs(registry);
   RegisterAnimationPolicyPrefs(registry);