The Cairo club popularly known as the White Knights won the delayed last-32 tie on away goals after losing the first leg 2-1 in Dakar last month.
Mohamed, a 21-year-old rising star, also scored in west Africa and that goal ultimately separated the clubs in a matchup Zamalek were expected to win more convincingly.
The five-time African champions go into Group A with Primeiro Agosto of Angola, Zesco United of Zambia and TP Mazembe of the Democratic Republic, another trophy holder on five occasions.
Zamalek start with an away match on November 29 or 30 against Mazembe, theoretically their toughest fixture in a section from which they should advance with the Congolese.
Mohamed scored after 19 minutes at the Al Salam Stadium in Cairo, sprinting past two slow-reacting defenders to poke a cross into the roof of the net from close range.
Generation Foot, an academy club whose former players include Liverpool and Senegal star Sadio Mane, were deprived of an equaliser just before half-time by a brilliant Mohamed Awad save.
Awad foiled the Senegalese side on several other occasions before being forced to retire with a neck injury midway through the second half.
Before he was replaced, Zamalek wasted a chance to increase their second leg lead when a fiercely struck Mahmoud Alaa penalty rebounded off the underside of the crossbar.
The second leg was originally scheduled for September 28, but the Senegalese refused to play when the match venue and date were changed by Zamalek at the last minute.
Generation will have a second shot at African glory this season as they drop to the CAF Confederation Cup, where they face ESAE of Benin in a play-off for a group place.