diff --git a/pcsx2-qt/MainWindow.cpp b/pcsx2-qt/MainWindow.cpp
index c9dfc6faad..e77b164252 100644
--- a/pcsx2-qt/MainWindow.cpp
+++ b/pcsx2-qt/MainWindow.cpp
@@ -897,7 +897,7 @@ void MainWindow::onGameListEntryContextMenuRequested(const QPoint& point)
 		QAction* action = menu.addAction(tr("Properties..."));
 		action->setEnabled(!entry->serial.empty());
 		if (action->isEnabled())
-			connect(action, &QAction::triggered, [entry]() { SettingsDialog::openGamePropertiesDialog(entry, entry->crc); });
+			connect(action, &QAction::triggered, [entry]() { SettingsDialog::openGamePropertiesDialog(entry, entry->serial, entry->crc); });
 
 		action = menu.addAction(tr("Open Containing Directory..."));
 		connect(action, &QAction::triggered, [this, entry]() {
@@ -1074,14 +1074,14 @@ void MainWindow::onViewGamePropertiesActionTriggered()
 		const GameList::Entry* entry = GameList::GetEntryForPath(m_current_disc_path.toUtf8().constData());
 		if (entry)
 		{
-			SettingsDialog::openGamePropertiesDialog(entry, entry->crc);
+			SettingsDialog::openGamePropertiesDialog(entry, entry->serial, entry->crc);
 			return;
 		}
 	}
 
 	// open properties for the current running file (isn't in the game list)
 	if (m_current_game_crc != 0)
-		SettingsDialog::openGamePropertiesDialog(nullptr, m_current_game_crc);
+		SettingsDialog::openGamePropertiesDialog(nullptr, m_current_game_serial.toStdString(), m_current_game_crc);
 }
 
 void MainWindow::onGitHubRepositoryActionTriggered()
diff --git a/pcsx2-qt/Settings/SettingsDialog.cpp b/pcsx2-qt/Settings/SettingsDialog.cpp
index fe00f6c5aa..7d6b29cef4 100644
--- a/pcsx2-qt/Settings/SettingsDialog.cpp
+++ b/pcsx2-qt/Settings/SettingsDialog.cpp
@@ -414,7 +414,7 @@ void SettingsDialog::setStringSettingValue(const char* section, const char* key,
 	g_emu_thread->applySettings();
 }
 
-void SettingsDialog::openGamePropertiesDialog(const GameList::Entry* game, u32 crc)
+void SettingsDialog::openGamePropertiesDialog(const GameList::Entry* game, const std::string_view& serial, u32 crc)
 {
 	// check for an existing dialog with this crc
 	for (SettingsDialog* dialog : s_open_game_properties_dialogs)
@@ -427,8 +427,8 @@ void SettingsDialog::openGamePropertiesDialog(const GameList::Entry* game, u32 c
 		}
 	}
 
-	std::unique_ptr<INISettingsInterface> sif =
-		std::make_unique<INISettingsInterface>(Path::Combine(EmuFolders::GameSettings, StringUtil::StdStringFromFormat("%08X.ini", crc)));
+	std::string filename(VMManager::GetGameSettingsPath(serial, crc));
+	std::unique_ptr<INISettingsInterface> sif = std::make_unique<INISettingsInterface>(std::move(filename));
 	if (FileSystem::FileExists(sif->GetFileName().c_str()))
 		sif->Load();
 
diff --git a/pcsx2-qt/Settings/SettingsDialog.h b/pcsx2-qt/Settings/SettingsDialog.h
index e6a4efb81c..0cf4f4e16c 100644
--- a/pcsx2-qt/Settings/SettingsDialog.h
+++ b/pcsx2-qt/Settings/SettingsDialog.h
@@ -50,7 +50,7 @@ public:
 	SettingsDialog(std::unique_ptr<SettingsInterface> sif, const GameList::Entry* game, u32 game_crc);
 	~SettingsDialog();
 
-	static void openGamePropertiesDialog(const GameList::Entry* game, u32 crc);
+	static void openGamePropertiesDialog(const GameList::Entry* game, const std::string_view& serial, u32 crc);
 
 	__fi bool isPerGameSettings() const { return static_cast<bool>(m_sif); }
 	__fi SettingsInterface* getSettingsInterface() const { return m_sif.get(); }
diff --git a/pcsx2/VMManager.cpp b/pcsx2/VMManager.cpp
index 3b6e39b279..b2b24419f0 100644
--- a/pcsx2/VMManager.cpp
+++ b/pcsx2/VMManager.cpp
@@ -285,9 +285,14 @@ void VMManager::ApplyGameFixes()
 	s_active_game_fixes += game->applyGSHardwareFixes(EmuConfig.GS);
 }
 
-std::string VMManager::GetGameSettingsPath(u32 game_crc)
+std::string VMManager::GetGameSettingsPath(const std::string_view& game_serial, u32 game_crc)
 {
-	return Path::Combine(EmuFolders::GameSettings, StringUtil::StdStringFromFormat("%08X.ini", game_crc));
+	std::string sanitized_serial(game_serial);
+	Path::SanitizeFileName(sanitized_serial);
+
+	return game_serial.empty() ?
+			   Path::Combine(EmuFolders::GameSettings, fmt::format("{:08X}.ini", game_crc)) :
+               Path::Combine(EmuFolders::GameSettings, fmt::format("{}_{:08X}.ini", sanitized_serial, game_crc));
 }
 
 void VMManager::RequestDisplaySize(float scale /*= 0.0f*/)
@@ -341,7 +346,13 @@ bool VMManager::UpdateGameSettingsLayer()
 	std::unique_ptr<INISettingsInterface> new_interface;
 	if (s_game_crc != 0)
 	{
-		const std::string filename(GetGameSettingsPath(s_game_crc));
+		std::string filename(GetGameSettingsPath(s_game_serial.c_str(), s_game_crc));
+		if (!FileSystem::FileExists(filename.c_str()))
+		{
+			// try the legacy format (crc.ini)
+			filename = GetGameSettingsPath({}, s_game_crc);
+		}
+
 		if (FileSystem::FileExists(filename.c_str()))
 		{
 			Console.WriteLn("Loading game settings from '%s'...", filename.c_str());
diff --git a/pcsx2/VMManager.h b/pcsx2/VMManager.h
index 227d980389..8e516be542 100644
--- a/pcsx2/VMManager.h
+++ b/pcsx2/VMManager.h
@@ -141,7 +141,7 @@ namespace VMManager
 	bool IsGSDumpFileName(const std::string& path);
 
 	/// Returns the path for the game settings ini file for the specified CRC.
-	std::string GetGameSettingsPath(u32 game_crc);
+	std::string GetGameSettingsPath(const std::string_view& game_serial, u32 game_crc);
 
 	/// Resizes the render window to the display size, with an optional scale.
 	/// If the scale is set to 0, the internal resolution will be used, otherwise it is treated as a multiplier to 1x.