The 22-year-old converted the 38th-minute kick to take Ghana above Mali in the Group B standings with four points from their opening two matches with a final group game against Niger to come in Port Elizabeth on Monday.
Wakaso was immediately booked after scoring for displaying a religious slogan when he lifted up his jersey to reveal "Allah is Great" emblazoned on his t-shirt.
It was his second yellow of the tournament and he will now miss Ghana's third group match against Niger on Monday.
The win was fully deserved after the Black Stars out-played the team who had beaten them to third place at the last finals in Equatorial Guinea and Gabon one year ago.
Emmanuel Agyemang Badu was a powerful presence in midfield and was at the heart Ghana's success. His run into the opposing area led to the penalty, just minutes after he had struck the upright with a header from Wakaso's free kick.
"We sought to try and change the tactics for an opponent with a different style of play," said Ghana coach Kwesi Appiah. "It proved successful."
It might have been a different story, however, had the Ivorian referee, Noumandiez Doue, shown a red card when Ghana goalkeeper Fatau Dauda handled just outside his area in the sixth minute.
Dauda slipped as he tried to claim the ball ahead of Mali's captain Seydou Keita and handled the ball on the ground, but escaped with a yellow card.
"I don't understand why the referee did not do his responsibility," said Mali coach Patrice Carteron.
Ghana dominated having made changes to their team after conceding a two-goal lead to draw their opening game against Democratic Republic of Congo on Sunday.
"We have to admit that Ghana was better than us today but we still have a last game to come," Carteron added.
"I'm sad for the players because we wanted to do better but we still have three points. We have no time to be disappointed now, we must prepare for the next game."
Mali, who beat Niger in their Group B opener, meet the Democratic Republic of Congo in their last match in Durban.
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