Libya was threatened with exclusion from the qualifiers if it failed to pay debts to their former coach Javier Clemente.

[4] Sierra Leone also faced possible exclusion from the qualifiers due to the suspension of their football association.

[11] The draw for the first round was held on 29 July 2019 at 12:00 EST (UTC+2), at the CAF headquarters in Cairo, Egypt.

[12][13] The draw for the second round was held on 21 January 2020, 19:00 CAT (UTC+2), at the Ritz-Carlton hotel in Cairo, Egypt.

The ten group winners from the second round were drawn into five home-and-away ties, with the teams seeded based on FIFA World Rankings.