Tarek Yehia’s side proved their Dark-Horse credentials and re-ignited the title race with a 79th minute winner from Moroccan substitute Omar Najdi.
The defeat froze Zamalek on 46 points, leveling with holders Ahli, but the Whites remained top on goal difference.
MCDR stretched their superb run to nine straight unbeaten games as they moved to sixth place with 34 points.
Ill-tempered
MCDR looked anything but afraid from the league leaders, with manager Yehia starting with two men upfront in Hussein Hamdi and Ivorian Oussou Konan.
But the visitors, who had four ex-Zamalek players in their starting line-up, were a bit edgy having collected three bookings inside the opening half hour.
MCDR's Hamdi was involved in a controversial incident which saw him handle the ball inside the six-yard box, but referee Yasser Mahmoud waved play on.
But in the 35th minute, the lanky striker received his marching orders after being adjudged to have punched Zamalek’s Hassan Mostafa.
The sending off hardly had an impact on the newcomers brave approach as Mohamed Thabet almost stunned Abdul-Wahed Al-Sayed before half time, only to see his long-range effort going agonizingly wide.
There was another moment of controversy before the break when Mohamed Abdul-Shafi's exquisite strike was ruled out for an offside, even though television replays showed the Zamalek defender was in a correct position.
Two chances…goal
Hossam Hassan introduced winger Hazem Emam for defensive midfielder Ibrahim Salah in an attempt to take advantage of the additional man.
However, MCDR surprisingly remained in charge and had a golden chance to break the deadlock through Konan, who went one-on-one with Abdul-Wahed before blasting the ball high with an poorly-attempted lob.
In the 68th minute, Yehia’s side made it clear they came for the three points as former Zamalek midfielder Ahmed Abdul-Raouf was denied by a superb save from Abdul-Wahed.
The goal that finished the game came in the 79th minute when full-back Fouad Salama whipped in a wicked cross that Abdul-Shafi failed to deal with, only for Najdi to bundle in past Abdul-Wahed from close range.
Zamalek went for another dramatic goal, but their attempts were limited to an 86th minute freekick by Shikabala, who was brilliantly denied by MCDR keeper Mostafa Kamal.