Jordan Ayew's solitary strike in the second half earned Ghana all three points in Sao Tome and Principe as they go top of Group C in the Nations Cup qualifier.
The Crystal Palace attacker stepped up to convert from the spot after Emmanuel Boateng was impeded by the Sao Tome goalie.
The Black Stars came close to grabbing the opener with two quick chances in the opening quarter of the game, after the Sao Tome goalkeeper's misplaced shot fell to Jordan Ayew, who laid the ball to Samuel Owusu.
Owusu's effort was deflected before Andy Yidom's ferocious strike was parried to corner by the Sao Tome shot stopper.
Ghana dominated the half with Real Mallorca midfielder Iddrissu Baba manning affairs in the heart of midfield.
Having controlled the first stanza, Ghana established their intent in the early seconds of the second half, as Thomas Partey headed wide from a Gideon Mensah cross.
Three minutes later a long range effort saw the Sao Tome goalkeeper fumbling to grab the ball, which was quickly picked up by Emmanuel Boateng before he was eventually fouled by the goalie to earn the Black Stars a penalty.
Jordan Ayew expertly converted sending the goalkeeper the wrong way.
Emmanuel Boateng was replaced by Kudus Mohammed before coach Kwesi Appiah handed Christopher Antwi-Adjei his debut after coming on to replace Samuel Owusu.
Ghana made several incursion from the flanks with Andy Yiadom and Gideon Mensah sending in the crosses.
The win sends Ghana top of Group C with six points and will next play Sudan in August of 2020.