diff --git a/code/gamesnd/gamesnd.cpp b/code/gamesnd/gamesnd.cpp
index cc3320a20a..ca8f981bd6 100644
--- a/code/gamesnd/gamesnd.cpp
+++ b/code/gamesnd/gamesnd.cpp
@@ -601,6 +601,7 @@ void gamesnd_unload_gameplay_sounds()
 			}
 		}
 	}
+	snd_unload_cleanup();
 }
 
 /**
@@ -636,6 +637,7 @@ void gamesnd_unload_interface_sounds()
 			}
 		}
 	}
+	snd_unload_cleanup();
 }
 
 void parse_gamesnd_old(game_snd* gs)
diff --git a/code/mission/missionmessage.cpp b/code/mission/missionmessage.cpp
index 70892eb0de..700f2ce484 100644
--- a/code/mission/missionmessage.cpp
+++ b/code/mission/missionmessage.cpp
@@ -1007,6 +1007,7 @@ void message_mission_shutdown()
 			snd_unload( Message_waves[i].num );
 		}
 	}
+	snd_unload_cleanup();
 
 	fsspeech_stop();
 
diff --git a/code/scripting/api/objs/sound.cpp b/code/scripting/api/objs/sound.cpp
index b30510079a..fd13f9115a 100644
--- a/code/scripting/api/objs/sound.cpp
+++ b/code/scripting/api/objs/sound.cpp
@@ -481,6 +481,7 @@ ADE_FUNC(unload, l_Soundfile, nullptr,
 		return ade_set_error(L, "b", false);
 
 	auto result = snd_unload(handle->idx);
+	snd_unload_cleanup();
 
 	if (result != 0) {
 		// Invalidate this handle so that the script cannot do something bad with it
diff --git a/code/sound/sound.cpp b/code/sound/sound.cpp
index 017e4f3b69..ae48ab9c81 100644
--- a/code/sound/sound.cpp
+++ b/code/sound/sound.cpp
@@ -481,6 +481,8 @@ sound_load_id snd_load(game_snd_entry* entry, int *flags, int /*allow_hardware_l
 	return sound_load_id(static_cast<int>(n));
 }
 
+static SCP_set<sound_load_id> Unloaded_sound_ids;
+
 // ---------------------------------------------------------------------------------------
 // snd_unload() 
 //
@@ -504,6 +506,8 @@ int snd_unload(sound_load_id n)
 
 	ds_unload_buffer(snd.sid);
 
+	Unloaded_sound_ids.emplace(n);
+
 	if (snd.sid != -1) {
 		Snd_sram -= snd.uncompressed_size;
 	}
@@ -530,6 +534,29 @@ void snd_unload_all()
 	while ( !Sounds.empty() ) {
 		snd_unload(sound_load_id((int)(Sounds.size() - 1)));
 	}
+	snd_unload_cleanup();
+}
+
+// If two tabled sounds share a sound file, unloading one will not correctly invalidate the index of the other,
+// causing a CTD when trying to play the other sound.
+// To fix this, every time we unload ANY sound, we must iterate over all tabled sounds, and invalidate their indices
+// if the given sound ID has been unloaded.
+void snd_unload_cleanup() {
+	for (auto& snd : Snds) {
+		for (auto& entry : snd.sound_entries) {
+			if (Unloaded_sound_ids.contains(entry.id)) {
+				entry.id = sound_load_id::invalid();
+			}
+		}
+	}
+	for (auto& snd : Snds_iface) {
+		for (auto& entry : snd.sound_entries) {
+			if (Unloaded_sound_ids.contains(entry.id)) {
+				entry.id = sound_load_id::invalid();
+			}
+		}
+	}
+	Unloaded_sound_ids.clear();
 }
 
 // ---------------------------------------------------------------------------------------
diff --git a/code/sound/sound.h b/code/sound/sound.h
index 18712092bd..567908e0d8 100644
--- a/code/sound/sound.h
+++ b/code/sound/sound.h
@@ -136,6 +136,7 @@ sound_load_id snd_load(game_snd_entry* entry, int* flags, int allow_hardware_loa
 
 int snd_unload(sound_load_id sndnum);
 void	snd_unload_all();
+void snd_unload_cleanup();
 
 // Plays a sound with volume between 0 and 1.0, where 0 is the
 // inaudible and 1.0 is the loudest sound in the game.