The Black Stars failed to break down Comoros in 0-0 draw at the Saïd Mohamed Cheikh International Stadium in Mitsamiouli.
Friday's Russia 2018 World Cup second qualifying round first leg tie saw Ghana go into the match as heavy favourites but a combination of dogged defending and some enterprising play from Comoros shocked the Stars.
The home side started well and could have put their noses in front under five minutes after Mohamed Soule struck the frame of the goal with a long-range shot.
The Islanders could have also carried the day after referee Norman Matemera disallowed a headed goal. Television replays showed the effort was actually onside.
Afriyie Acquah delivered a perfect diagonal pass to Afful who had made the run into the box but the right-back was spotted in an offside position on 18 minutes.
Andre Ayew, who was by far Ghana's best player on the day, was unlucky to nudge in a powerful cross from the right in one of those stodgy, periodic plays.
After an unproductive first half, Ghana upped the tempo and the substitution worked to perfection as Emmanuel Agyemang Badu and David Accam changed the complexion of the match.
Ghana came close to scoring in the last ten minutes. Twice in a matter of seconds they struke the frame of the Comoros goal, first through Emmanuel Agyemang-Badu, then through Andre Ayew.
The return leg will be played in Kumasi next Tuesday with the winner advancing to the third qualifying round which will involve 20 teams put into five groups of four.
Line-ups
Comoros: Ben Boina, Rachidi, Abdallah, Alhadhur, Mogni, M’Chamgama, Combo, Soule, Benjaloud, Chamed, Mohamed
Coach: Amir ABDOU (FRA)
Ghana: Braimah, H Afful, B Rahman, J Mensah, J Boye, A Acquah, S Asante, M Wakaso, J Ayew, AM Waris, A Ayew (c)
Coach: Avram GRANT (ISR)
Officials
Referee: Norman MATEMERA (ZIM)
Assistant Referee 1: Tapfumanei MUTENGWA (ZIM)
Assistant Referee 2: Salani NCUBE (ZIM)
Fourth Official: Ruzive RUZIVE (ZIM)
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