The 2020–21 CAF Confederation Cup (officially the 2020–21 Total CAF Confederation Cup for sponsorship reasons) was the 18th edition  of Africa's secondary club football tournament organized by the Confederation of African Football (CAF), under the current CAF Confederation Cup title after the merger of CAF Cup and African Cup Winners' Cup.
 The winners of the 2020–21 CAF Confederation Cup will earn the right to play against the winners of the 2020–21 CAF Champions League in the 2021–22 CAF Super Cup.
 RS Berkane were the defending champions, but were eliminated in the group stage.
 All 56 CAF member associations may enter the CAF Confederation Cup, with the 12 highest ranked associations according to their CAF 5-year ranking eligible to enter two teams in the competition. As a result, theoretically a maximum of 68 teams could enter the tournament (plus 16 teams eliminated from the CAF Champions League which enter the play-off round) – although this level has never been reached.
 For the 2020–21 CAF Confederation Cup, the CAF uses the 2016–2020 CAF 5-year ranking, which calculates points for each entrant association based on their clubs’ performance over those 5 years in the CAF Champions League and CAF Confederation Cup. The criteria for points are the following:
 The points are multiplied by a coefficient according to the year as follows:
 Due to the COVID-19 pandemic, associations may abandon their domestic competitions and select the representatives in CAF club competitions. Associations may register their representatives during the engagement window between 1 September and 20 October 2020. All engaged teams must respect the Club Licensing procedure and cooperate with their respective Associations, as non-licensed clubs would be refused participation.
 The following 51 teams from 39 associations entered the competition.
 Associations are shown according to their 2016–2020 CAF 5-year ranking – those with a ranking score have their rank and score (in parentheses) indicated.
 A further 16 teams eliminated from the 2020–21 CAF Champions League enter the play-off round.
 The start of the competition was delayed due to the COVID-19 pandemic. On 1 September 2020, the CAF announced the new schedule. On 10 September 2020, the CAF decided to further delay the preliminary round, originally scheduled for 20–22 November (first legs) and 27–29 November (second legs), and the first round, originally scheduled for 11–13 December (first legs) and 18–20 December (second legs).
 The original schedule of the competition, as planned before the pandemic, was as follows.
 The draw for the qualifying rounds was held on 9 November 2020 at the CAF headquarters in Cairo, Egypt.
 In the qualifying rounds, each tie will be played on a home-and-away two-legged basis. If the aggregate score is tied after the second leg, the away goals rule will be applied, and if still tied, extra time will not be played, and the penalty shoot-out will be used to determine the winner (Regulations III. 13 & 14).
 Notes:
 The 16 winners of the first round advance to the play-off round, where they will be joined by the 16 losers of the Champions League first round.
 Notes:
 The 15 winners of the play-off round will advance to the group stage to join RS Berkane, who advanced directly to the group stage as the winners of the first round with the best CAF 5-year ranking following Gazelle withdrawal from the competition after being transferred from the Champions League.
 The draw for the group stage was held on 22 February 2021, 13:00 GMT (15:00 local time, UTC+2), at the CAF headquarters in Cairo, Egypt. The 16 teams, which consist of the 15 winners of the play-off round of qualifying and defending champions RS Berkane, were drawn into four groups of four.
 The teams were seeded by their performances in the CAF competitions for the previous five seasons (CAF 5-year ranking points shown in parentheses). Each group contained one team from each of Pot 1, Pot 2, Pot 3, and Pot 4, and each team was allocated to the positions in their group according to their pot:
 In each group, teams play against each other home-and-away in a round-robin format. The winners and runners-up of each group will advance to the quarter-finals of the knockout stage.
 
 
 
 
 The mechanism of the draws for each round is as follows:
 The bracket was decided after the draw for the knockout stage (quarter-finals and semi-finals), which was held on 30 April 2021, 14:00 CAT (UTC+2), at the CAF headquarters in Cairo, Egypt.
 The final was played on 10 July 2021 at Stade de l'Amitié, Cotonou.