Myziane Maolida's first half strike was enough as Comoros stunned Ghana in the 2026 FIFA World Cup qualifier in Moroni.
The Black Stars named a changed side with Andre Ayew starting in place of the half fit Mohammed Kudus.
Despite getting off to a fine start, with Inaki Williams serving Antoine Semenyo the best opportunity of the half, Ghana failed to take the lead.
Comoros punished Ghana after Myziane Maolida broke through Ghana's defence to open the scoring in the 43rd minite.
Chris Hughton replaced Abdul Salis with Majeed Azhimeru in the second half as the Black Stars chased the game.
Ghana created some chances but the Comorians were hard to break.
In the final moments, the hosts defended resolutely to beat Ghana for the second time.
The victory sends Comoros top of Group I while Ghana sit third behind Mali.
Ghana will face Mali in June as the World Cup qualifiers continue next year.