Later, Ghana snatched a late 1-1 draw with Cameroon in the second match of a Group A double-header at the 75,000-capacity Cairo International Stadium.
Franck Evina, who is on the books of Bayern Munich and known as the 'Bavarian Hulk', put Cameroon ahead after 59 minutes and substitute Mohammed Habib levelled three minutes from time.
Forward Mohamed has earned rave reviews for his performances with top Egyptian club Zamalek at home and in Africa, with some pundits comparing him to legendary forward Hossam Hassan.
He made an immediate impact in the tournament as he not only got his country off to a perfect start, but was also voted man of the match.
Egypt are desperate to secure a top-three finish and a passport to Japan after the senior national team flopped as hosts of the 2019 Africa Cup of Nations.
A Pharaohs team boasting Liverpool star and twice African Footballer of the Year Mohamed Salah suffered a shock last-16 loss to South Africa in a tournament won by Algeria.
Mohamed struck on 29 minutes, powerfully heading an Ahmed Abo Elfetouh cross past Mali goalkeeper Youssouf Koita into the corner of the net.
Fellow Egypt forward Nasser Maher was forced to retire early in the second half with a shoulder injury, but his team-mates comfortably contained Mali to go top of the table.
Cameroon, coached by Indomitable Lions great Rigobert Song, were poised to join Egypt on three points thanks to an Evina goal direct from a free-kick against Ghana.
Evina is on loan to German third tier club KFC Uerdingen 05 this season from four-time European champions Bayern Munich.
But Habib salvaged a draw for the Black Meteors by poking the ball past Cameroon goalkeeper Simon Omossola after a deflected long-range shot looped into his path.
Stephane Zobo, who replaced an exhausted Evina 14 minutes from time, wasted a chance to win the match in stoppage time when he headed a Michael Cheukoua cross wide.
Group B starts Saturday at the 30,000-seat Al Salam Stadium with a match between Nigeria and the Ivory Coast, followed by South Africa against Zambia.
South Africa have been hampered by the refusal of some domestic clubs to free players ahead of the November 11-19 international window, and will face Zambia with a squad of only 15.
All the contenders have played at the Olympics with Egypt making 11 appearances, Nigeria seven, Ghana six, Cameroon three, South Africa and Zambia two and Ivory Coast and Mali one.