The Pharaohs, who last took part in the Nations Cup when they lifted a record seventh trophy in 2010, struggled for rhythm throughout and allowed Mali to lay siege to their area for long periods at the Port Gentil Stadium in Gabon, although goal-scoring chances were few and far between.
The only highlight of a drab affair was a new record set by Egypt's veteran keeper Essam El-Hadary, who became the oldest player in the tournament's history when he replaced Zamalek's injured guardian Ahmed El-Shennawi in the first half.
Earlier in the day, Ghana claimed a narrow 1-0 victory over Uganda to go top of Group D.
Egypt were largely sluggish in the final third and were eventually unable to unlock a watertight Malian defence.
They next face Uganda on Saturday before meeting powerhouses Ghana in their final group stage game four days later.
Although Egypt created the game's first chance after five minutes when lone striker Marwan Mohsen swiveled past his marker and had an angled shot blocked by keeper Oumar Sissoko, it was Mali who had the upper hand in the first half.
Egypt were pegged back by relentless pressing from the Malians, whose physical attributes made it hard for them to win any aerial challenges.
Mohamed Salah, who often shoulders the responsibility of finishing off any breakaways, was well shackled and Abdallah El-Said's usual defence-splitting passes were nowhere to be seen.
But for all Mali's dominance, they hardly created clear-cut chances apart from a cross-cum-shot from burly forward Moussa Marega which forced a superb save from Ahmed El-Shennawi with his finger tips.
However, the Zamalek keeper shed tears when he was replaced on 24 minutes after hurting his hamstring, making way for the 44-year-old El-Hadary, who beat the record of former teammate Hossam Hassan who was 39 when he took part in the 2006 edition.
While Egypt preferred to sit back and soak up pressure before the break, adhering to coach Hector Cuper's strict defensive strategy, they grew bolder in the second half to gain more possession and push forward.
They could have opened the scoring on 53 minutes when a diagonal cross from winger Mahmoud Trezeguet found the unmarked Mohsen, whose header was blocked by Sissoko.
Salah, who failed to make an impact, and Mohsen were replaced by Stoke City winger Ramadan Sobhi and Sporting Braga striker Ahmed Kouka respectively as Cuper sought to beef up his attack.
But the substitutions were to no avail, with both sides struggling to string passes together on a muddy pitch in the final stages.
Mali had a chance though with 11 minutes remaining when Ousmane Coulibaly headed a flick from Salif Coulibaly over the crossbar.
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