diff --git a/src/core/settings.cpp b/src/core/settings.cpp
index eccfd576f..723667b91 100644
--- a/src/core/settings.cpp
+++ b/src/core/settings.cpp
@@ -168,6 +168,7 @@ void Settings::Load(SettingsInterface& si)
   create_save_state_backups = si.GetBoolValue("Main", "CreateSaveStateBackups", true);
   confim_power_off = si.GetBoolValue("Main", "ConfirmPowerOff", true);
   load_devices_from_save_states = si.GetBoolValue("Main", "LoadDevicesFromSaveStates", false);
+  apply_compatibility_settings = si.GetBoolValue("Main", "ApplyCompatibilitySettings", true);
   apply_game_settings = si.GetBoolValue("Main", "ApplyGameSettings", true);
   auto_load_cheats = si.GetBoolValue("Main", "AutoLoadCheats", true);
   disable_all_enhancements = si.GetBoolValue("Main", "DisableAllEnhancements", false);
@@ -385,6 +386,7 @@ void Settings::Save(SettingsInterface& si) const
   si.SetBoolValue("Main", "CreateSaveStateBackups", create_save_state_backups);
   si.SetBoolValue("Main", "ConfirmPowerOff", confim_power_off);
   si.SetBoolValue("Main", "LoadDevicesFromSaveStates", load_devices_from_save_states);
+  si.SetBoolValue("Main", "ApplyCompatibilitySettings", apply_compatibility_settings);
   si.SetBoolValue("Main", "ApplyGameSettings", apply_game_settings);
   si.SetBoolValue("Main", "AutoLoadCheats", auto_load_cheats);
   si.SetBoolValue("Main", "DisableAllEnhancements", disable_all_enhancements);
diff --git a/src/core/settings.h b/src/core/settings.h
index 325ee22c5..244a07d05 100644
--- a/src/core/settings.h
+++ b/src/core/settings.h
@@ -70,6 +70,7 @@ struct Settings
   bool create_save_state_backups = false;
   bool confim_power_off = true;
   bool load_devices_from_save_states = false;
+  bool apply_compatibility_settings = true;
   bool apply_game_settings = true;
   bool auto_load_cheats = true;
   bool disable_all_enhancements = false;
diff --git a/src/core/system.cpp b/src/core/system.cpp
index 941718279..b92eb0c16 100644
--- a/src/core/system.cpp
+++ b/src/core/system.cpp
@@ -825,7 +825,7 @@ void System::LoadSettings(bool display_osd_messages)
   Host::LoadSettings(si, lock);
 
   // apply compatibility settings
-  if (g_settings.apply_game_settings && !s_running_game_code.empty())
+  if (g_settings.apply_compatibility_settings && !s_running_game_code.empty())
   {
     const GameDatabase::Entry* entry = GameDatabase::GetEntryForSerial(s_running_game_code);
     if (entry)
@@ -848,6 +848,14 @@ void System::ApplySettings(bool display_osd_messages)
   const Settings old_config(std::move(g_settings));
   g_settings = Settings();
   LoadSettings(display_osd_messages);
+
+  // If we've disabled/enabled game settings, we need to reload without it.
+  if (g_settings.apply_game_settings != old_config.apply_game_settings)
+  {
+    UpdateGameSettingsLayer();
+    LoadSettings(display_osd_messages);
+  }
+
   CheckForSettingsChanges(old_config);
   Host::CheckForSettingsChanges(old_config);
 
@@ -867,7 +875,7 @@ bool System::ReloadGameSettings(bool display_osd_messages)
 bool System::UpdateGameSettingsLayer()
 {
   std::unique_ptr<INISettingsInterface> new_interface;
-  if (!s_running_game_code.empty())
+  if (g_settings.apply_game_settings && !s_running_game_code.empty())
   {
     std::string filename(GetGameSettingsPath(s_running_game_code));
     if (FileSystem::FileExists(filename.c_str()))
diff --git a/src/duckstation-qt/advancedsettingswidget.cpp b/src/duckstation-qt/advancedsettingswidget.cpp
index 678c6a8fc..e1b7e5aec 100644
--- a/src/duckstation-qt/advancedsettingswidget.cpp
+++ b/src/duckstation-qt/advancedsettingswidget.cpp
@@ -201,10 +201,12 @@ AdvancedSettingsWidget::AdvancedSettingsWidget(SettingsDialog* dialog, QWidget*
 
   addBooleanTweakOption(dialog, m_ui.tweakOptionTable, tr("Disable All Enhancements"), "Main", "DisableAllEnhancements",
                         false);
-  addBooleanTweakOption(dialog, m_ui.tweakOptionTable, tr("Show Status Indicators"), "Display", "ShowStatusIndicators",
-                        true);
   addBooleanTweakOption(dialog, m_ui.tweakOptionTable, tr("Show Enhancement Settings"), "Display", "ShowEnhancements",
                         false);
+  addBooleanTweakOption(dialog, m_ui.tweakOptionTable, tr("Show Status Indicators"), "Display", "ShowStatusIndicators",
+                        true);
+  addBooleanTweakOption(dialog, m_ui.tweakOptionTable, tr("Apply Compatibility Settings"), "Main",
+                        "ApplyCompatibilitySettings", true);
   addIntRangeTweakOption(dialog, m_ui.tweakOptionTable, tr("Display FPS Limit"), "Display", "MaxFPS", 0, 1000, 0);
 
   addMSAATweakOption(dialog, m_ui.tweakOptionTable, tr("Multisample Antialiasing"));
@@ -281,8 +283,9 @@ void AdvancedSettingsWidget::onResetToDefaultClicked()
   int i = 0;
 
   setBooleanTweakOption(m_ui.tweakOptionTable, i++, false);    // Disable all enhancements
-  setBooleanTweakOption(m_ui.tweakOptionTable, i++, true);     // Show status indicators
   setBooleanTweakOption(m_ui.tweakOptionTable, i++, false);    // Show enhancement settings
+  setBooleanTweakOption(m_ui.tweakOptionTable, i++, true);     // Show status indicators
+  setBooleanTweakOption(m_ui.tweakOptionTable, i++, true);     // Apply compatibility settings
   setIntRangeTweakOption(m_ui.tweakOptionTable, i++, 0);       // Display FPS limit
   setChoiceTweakOption(m_ui.tweakOptionTable, i++, 0);         // Multisample antialiasing
   setBooleanTweakOption(m_ui.tweakOptionTable, i++, false);    // PGXP vertex cache