The White Knights took the lead in the 43rd minute through a Youssef Obama header before Abdallah El-Saied doubled their advantage from the penalty spot shortly after halftime.
Ahmed Magdy, however, gifted Talae El-Geish a lifeline with an own goal in the second half, but Zamalek held on to secure their second consecutive win.
The victory propels Zamalek to fifth place in the standings with 44 points from 25 matches, keeping their golden square aspirations alive.
Talae El-Geish, meanwhile, remain in 11th with 35 points.
This win comes after Zamalek defeated Ismaily 2-1 in the previous round. However, their opponents, Talae El-Geish, faced a gruelling schedule, playing both Ahly and Zamalek within three days, suffering a 2-0 defeat to the Red Devils before Thursday's encounter.
Zamalek will be looking to build on this momentum as they continue their push for a higher finish in the Egyptian Premier League.
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