All matches were played between 11 and 24 February 2021, except matches involving teams participating in African competitions (Al Ahly, Pyramids and Zamalek) were postponed and played on 13 March and 14 April 2021. This round includes one team from the Egyptian Fourth Division, La Viena, the lowest ranking side left in the competition. La Viena also became the first club from the lowest league in the Egyptian football league system to qualify for the main round of the Egypt Cup in the competition's history; having participated in all preliminary qualifying rounds.