Egyptian Premier League side Al Ahly are the defending champions, having defeated Tala'ea El Gaish in the final.
The competition was originally scheduled to start in November 2020, but was postponed to early 2021 due to the COVID-19 pandemic in Egypt.
The draw for the main competition was held at the Egyptian Football Association headquarters in Gezira, Cairo on 6 February 2021.
Usually, the Egypt Cup defending champions and the Egyptian Premier League winners are placed in different paths, so both teams can face each other only in the final.
This round includes one team from the Egyptian Fourth Division, La Viena, the lowest ranking side left in the competition.
One match involving two teams from the Egyptian Second Division was moved to 8 March 2021 to avoid scheduling conflicts, while unconfirmed matches at that time (involving winning teams from round of 32 fixtures featuring Al Ahly, Pyramids and Zamalek) were postponed to a later date.
This round included two teams from the Egyptian Second Division, Coca-Cola and Petrojet, the lowest ranking sides left in the competition.
This round includes one team from the Egyptian Second Division, Petrojet, the lowest ranking side left in the competition.
This round includes one team from the Egyptian Second Division, Petrojet, the lowest ranking side left in the competition.