The draw has produced two heavyweight encounters, leaving four of South African football's biggest clubs needing just one more victory to book their place in the final.
Sundowns and Chiefs will headline the semi-final fixtures when they meet in Pretoria, with both sides having plenty of motivation to progress to the next round.
The Brazilians will be desperate to put their recent disappointment behind them after suffering a 3-1 defeat against USM Alger in the CAF Super Cup at Loftus Versfeld Stadium.
Miguel Cardoso's charges will now shift their focus to domestic competition as they look to keep their hopes of adding their first trophy of the season to their cabinet alive.
Chiefs, meanwhile, head into the encounter with renewed confidence after securing a 2-1 comeback victory over Siwelele FC in the quarter-finals.
Amakhosi found themselves trailing after conceding an early goal but managed to turn the contest around through Wandile Duba, who converted a penalty on the stroke of half-time.
Substitute Asanele Velebayi then proved to be the match-winner, finding the back of the net in the 84th minute to secure Chiefs' place in the last four.
In the other semi-final, Pirates will face Stellenbosch in what promises to be a challenging assignment for the defending champions.
The Buccaneers booked their place in the last four following a hard-fought 1-0 victory over Sekhukhune United at Orlando Amstel Arena on Saturday.
Teenage forward Mpho Padime scored the decisive first-half goal to send Abdeslam Ouaddou's men through and keep their hopes of retaining the trophy alive.
The matches are scheduled to take place on the weekend of November 21-22 with times and venues to be announced.
Mamelodi Sundowns head coach Miguel Cardoso has admitted that his team struggled to impose their usual style of football during their 3-1 defeat to USM Alger in the CAF Super Cup.
Orlando Pirates coach Abdeslam Ouaddou believes Sifiso Luthuli has a bright future at the club, backing the striker to become an important figure in the Buccaneers' attack.
The PSL has announced AmaZulu coach Arthur Zwane, Orlando Pirates midfielder Thapelo Mokobodi and Mamelodi Sundowns star Teboho Mokoena as individual award winners for September/October.
Asanele Velebayi is beginning to make his presence felt at Kaizer Chiefs, with head coach Fernando da Cruz delighted by the midfielder's ability to deliver despite limited playing time.
