كتب : Mohamed Sabe
Fresh-promoted Olympic took a stunning lead in the seventh minute through Ahmed Adel but Zamalek finished the first period in front after a brace from Abdul-Halim Ali in the 14th and 20th minutes.
Second-half headers from Mostafa Gaafar and Mohamed Sedik in the 57th and 86th minutes respectively sealed the big victory for the visitors and lift Zamalek to play Suez Cement in the next round.
Earlier on Tuesday, A brilliant strike from midfielder Ahmed Hassan gave Ahli a 1-0 over Bani Swaif Telecom in their Egypt Cup round of 32 match.
Hassan struck home from long range in the 13th minute to send the Egyptian champions to the Egypt Cup round of 16.
Ahli gave a mediocre performance throughout the game as Bani Swaif proved to be worthy contenders.
Elsewhere, Ismaili booked their round of 16 ticket with a 2-1 away win over Tanta.
Ahmed Fathi and Sherif Abdul-Fadil scored Ismaili's goals before Mohab Saied pulled one back for the hosts.
Meanwhile, Masri crushed local side Rebaat & Anwaar 3-1 to move to the next round.
Suez Cement also advanced to the round of 16 with a 2-0 win over Asyut Petroleum, courtesy of extra time goals from Ahmed Omran and Mohamed Khafagi.
In other matches, Al-Mustaqbal pulled a surprise by eliminating Premier League side Asyut Cement with a 2-1 win, Aluminum edged past Al-Nassr with a 1-0 win and Arab Contractors beat Samanoud 2-0.