Didier Drogba scored his second goal of the tournament early in the first-half to put Ivory Coast ahead.
Marc Zoro extended the gap and substitute Boubacar Sanogo completed the rout late in the match.
In the other Group B match, John Obi Mikel put Nigeria in front seven minutes after the interval when he headed home Peter Odemwingie's chipped-cross.
Everton striker Yakubu Aiyegbeni ensured the victory four minutes before the final whistle when he went one-on-one with the keeper before slotting into the net.
Ivory Coast finished as Group B winners with nine points from three matches. They will face Guinea in the quarter-finals.
Nigeria qualified to the next round due to their superior goal difference to Mali as both teams have four points.
The two-time African champions will have a tough task to reach the semis as they will play hosts Ghana.
Elephants Ease Past Mali
Drogba opened the scoring after nine minutes when he latched onto Koffi Ndri's deft pass inside the area before curling a low shot into the far bottom corner.
Despite risk missing out on a place in the quarter-finals, Mali did not look determined to overturn the deficit as they failed to impose any threat in the first-half.
Ivory Coast defender Zoro should have doubled the lead in the 19th minute when he rose unmarked to meet Ndri's corner but his header missed the target from six yards.
Arouna Kone also missed a golden opportunity in the 28th minute after failing to head Siaka Tiene's left-wing cross goalwards although he was under no pressure.
Mail failed to break through Ivory Coast's powerful defense but had a decent chance from a set-piece two minutes after restart.
Seydou Keita curled the free-kick round the wall but keeper Boubacar Barry was on alert to parry the ball.
Mali hopes were dealt a huge blow when Zoro added the second after towering at the near post to head past Mahamadou Sidibe in the 50th minute.
They were downhearted after learning that Nigeria went ahead of Benin through John Obi Mikel.
Mali were unfortunate not to narrow the gap in the 68th minute when a mis-timed jump by Barry allowed Dramane Traore to head towards an open net but his effort was denied by the bar.
Substitute Sanogo killed off Mali hopes five minutes from time when he scored from the rebound after Yaya Toure's initial shot was poorly blocked by Sidibe.