Mohamed Ibrahim scored the opening goal from a penalty shortly before half time as the Whites had to wait until the 83rd minute to find the net again.
It was summer signing Momen Zakaria who scored a goal that could prove vital when both sides re-clash in the second leg.
Zakaria's goal relieved more than 10000 supporters at Cairo Stadium, which hosted a continental game for Zamalek for the first time in years.
The retrun game takes place after two weeks in Niamey.
Should Zamalek win, they will meet the winner of the tie between Angola's Kabuscorp and Cote d'Or of Seychelles later this month.
VIDEO HIGHLIGHTS
Ibrahim scores from the spot after youngster Mostafa Fathi was tackled in the box.
Zakaria scores the second after a fine assist by Ahmed Gaafar.