The Black Stars failed to go top of Group I after suffering a narrow defeat to Comoros
Ahead of the game, Chris Hughton made three changes in the squad that defeated Madagascar 1-0 in the opening game at the Baba Yara Sports Stadium last Friday.
West Ham United star midfielder Kudus Mohammed could not pass a late fitness test and as a result Andre Ayew took his place.
Also, defenders Daniel Amartey and Alidu Seidu were dropped for Kassim Nuhu and Denis Odoi respectively.
Jordan Ayew came close to opening the scoring in the first half when he rose to head a cross wide.
Few minutes later, Inaki Williams saw his shot blocked before another chance from Antoine Semenyo was blocked.
Comoros scored the opener on 43rd minute through M. Maolida to send the home fans into wild jubilation.
After the break, Ghana made several changes with Kudus, Nuamah and others coming on board but the hosts were resilient at the back and held on to record a memorable victory.
With Mali sharing the spoils 1-1 with Central African Republic at home while Madagascar brushed aside Chad yesterday, the win for Comoros have seen them going top of the log with six points from two games.
Ghana are now third on log with three points while Mali sit second with four points.