Young Nigerian striker Victory Beniangba, 18, stunned the title holders with a goal on the break 20 minutes from time as Zamalek were punished for another listless display at Cairo's International Stadium.
It was their second defeat in seven days after they lost 2-0 to Enppi following a three-match winning run.
Although Zamalek are still on top with 41 points, second-placed Pyramids (39 points) can leapfrog them if they win their match in hand while third-placed Ahly (33 points) can go seven points clear of them if they win their five rescheduled matches.
El-Geish, who extended their unbeaten run to 11 matches, moved up to seventh with 26 points.
El-Geish surprisingly took the game to Zamalek in the first half, adopting a high pressing strategy and creating an early chance when a poor defensive clearance fell to winger Ahmed Samir, whose half-volley forced a fine save from keeper Mohamed Awad.
Zamalek struggled to get going as they lacked spark in the final third, with key Moroccan winger Achraf Bencharki starting on the bench.
It took them until the cusp of halftime to create their first opportunity as the introduction of pacy right-back Hazem Emam, who replaced Hamza Mathlouthi after the Tunisian picked up an injury, injected zeal.
Central defender Mahmoud El-Wensh headed over the bar from a good scoring position in a rare Zamalek effort before El-Geish altered their strategy after the restart, sitting back to soak up pressure.
Zamalek could have scored three minutes into the second half when a mistake from defender Mostafa El-Zannari allowed striker Omar El-Said to break clear, only to blast his shot high over.
Winger Ahmed Zizo also volleyed just wide after being found unmarked by a left-wing cross from Bencharki, who came on in the second half.
However, El-Geish scored against the run of play on 70 minutes when, from a counter attack, Ahmed Samir slipped a pass that eluded poorly-positioned defender Mohamed Abdel-Ghani and released Beniangba to fire home past the advancing Awad.
Zamalek's late pressure yielded some half-chances that they could not take as El-Geish claimed a famous win to dent the hopes of their illustrious opponents to defend their league crown.
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