There was very little action in the game until Emmanuel Agyemang-Badu struck the post with a header in the 32nd minute.
It was Badu who won the penalty that put the Black Stars ahead just six minutes later.
The referee awarded a penalty for Adama Tamboura's sliding challenge, and Wakaso stepped up to take it.
Mali keeper Mamadou Samassa guessed the right way, but there was too much power on the winger's shot.
Ghana had chances to stretch their lead in the second half, with Bristol City winger Albert Adomah nearly finding Asamoah Gyan unmarked at the back post, while Samassa was forced to save Badu's long-range effort.
In the end, it was a comfortable win for James Kwesi Appiah's side, who face Niger in their final group game.