The draw was conducted on Friday ahead of the 2021/22 season which will start next month
Mamelodi Sundowns and Orlando Pirates have both been given a bye in the preliminary round of Caf's inter-club tournaments.
Sundowns are one of the top-ranked sides in the Caf Champions League and they have been exempted from the preliminary round of Africa's most prestigious club tournament.
The Tshwane giants, who won the Champions League in 2016, will take part in the first round having qualified for the competition after winning the 2020/21 PSL title.
They will await the winner of the preliminary round tie between Gabonese champions Bouenguidi Sports and DR Congolese side AS Maniema Union.
While AmaZulu FC have been pitted against Malawian giants Nyasa Big Bullets in what will be their debut appearance in the Champions League.
Usuthu will take on five-time Champions League winners Tout Puissant Mazembe of DR Congo in the first round tie if they overcome Big Bullets.
AmaZulu secured their spot in the competition after finishing second in the PSL last season under the guidance of their Uefa Champions League-winning coach Benni McCarthy.
Meanwhile, Pirates have been given a bye in the Caf Confederation Cup preliminary round due to their ranking after qualifying for Africa's secondary club tournament as third-place finishers in the PSL last term.
The Buccaneers, who reached last season's Confederation Cup quarter-finals, will take on the winner between Burundian side Bumamuru FC and Congo-Brazzaville outfit Diables Noirs in the first round tie.
While tournament debutants Marumo Gallants are set to take on Futuro Kings from Equatorial Guniea in the preliminary round.
Gallants (formerly known as Tshakhuma Tsha Madzivhandila) qualified for the Confederation Cup after winning the Nedbank Cup last season.
The preliminary round matches for both the Champions League and Confederation Cup will be played next month.
The first-round ties are scheduled to take place in October this year.
Full Caf inter-club draw