The 85th minute effort proved the difference at the Amahoro Stadium in Kigali.
With the Amavubi seeing the back of the Black Stars in their last encounter in a 2004 Afcon qualifier courtesy of a solitary Jimmy Gatete strike, Ghana were as much on a revenge mission.
Andre Ayew returned to the starting XI for the first time since March, as captain in the absence of the injured Asamoah Gyan, whose place was taken up by Richmond Boakye-Yiadom, while Afriyie Acquah and Jordan Ayew both earned starting spots despite recent controversies surrounding the duo and the Torino man’s wife.
Rwanda coach Johnny McKinstry also kept faith in the likes of goalkeeper Olivier Kwizera, Quentin Rushenguziminega and Jean-Claude Iranzi after his side’s 3-1 win over Ethiopia in a warm-up fixture.
A pockmarked pitch became the undoubted challenge as both sides struggled to control the ball in the opening minutes.
In that, a harmless Daniel Amartey free header from a Wakaso corner kick after six minutes, and a coolly collected Christian Atsu effort from range remained the only attempts on goal in the first half hour as both sides resorted to ballooning the ball up and out than to control.
Wakaso drove in a long cross from a free-kick on 31 minutes but Andre Ayew, under pressure from his marker, failed to direct his header on goal.
Back from recess after a boring first half, Rwanda appeared to have upped the ante, Rushenguziminega seeing a penalty call ignored on the 49th minute after a challenge in the Ghana box.
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Rwanda’s push seemingly challenged the Ghanaians to respond, as Avram Grant sought to add more speed to his attack with the introduction of Solomom Asante for Boakye on 60 minutes.
It almost paid off two minutes later as Atsu beat his marker before firing a shot which Kwizera parried wide, after which Jordan Ayew saw a free-kick fly wide off target on 70 minutes.
Asante then had a beautiful chance, perhaps the best on the day,to put Ghana ahead after he was neatly set up by Jordan Ayew, but the substitute blasted his shot in the 18-yard box way off target.
But then, the decider was to come shortly, as Mubarak Wakaso curled in a neat free kick beyond the reach of Kwizera to give Ghana the lead on 85 minutes.
The Amavubi tried to launch a late challenge in the closing stages, but were not able to make use of a further four-minute injury time addition, as Grant led his men to a memorable revenge in Kigali.