The Black Stars have four points while Mali slipped to second place on three points on Thursday.
Democratic Republic of Congo, who have collected one point, face pointless Niger later in the second game of a Nelson Mandela Bay Stadium double-header.
Ghana dominated this encounter with Mali lacking the firepower to trouble their opponents even after the introduction of fit-again West Ham striker Modibo Maiga.
Mubarak Wakaso put Ghana in front from the penalty spot in the 38th minute after the lively Emmanuel Agyemang Badu was brought down inside the box by experienced left-back Adama Tamboura.
Wakaso will miss his team's final group game on Monday against Niger after he was booked for his celebration – his second caution of the competition.
This was the third time the west African countries clashed in the tournament within a year.
Ghana won a group game 2-0 in Gabon at the 2012 tournament before Mali gained revenge by winning 2-0 to clinch third place.
Ghana take it to the top
In a cautious first half, Ghana created more chances.
After eight minutes, Mali skipper Seydou Keita's free kick from the top of the box, after goalkeeper Fatau Dauda handled outside his area, narrowly missed the target with the goalkeeper beaten. Thereafter, it was Ghana all the way.
On 13 minutes, Black Stars skipper Asamoah Gyan saw his shot from inside the box blocked for a corner.
Badu's header in the 32nd minute off a Wakaso free kick came back off the foot of the post with Mali goalkeeper Mamadou Samassa beaten.
Mali began the second half brightly and veteran Keita just failed to connect with a clever chip by Mahamane Traoré, who had a shot tipped over by Dauda.
A Wakaso free kick was not far off target and a Gyan shot nearly caught the Mali goalkeeper napping.
Badu had a free kick scrambled away for a corner and substitute Solomon Asante almost made an immediate impact when he latched on to a loose ball only to miss. – Sapa-AFP