Chiefs will host their Soweto rivals in November after overcoming Cape Town City in a penalty shoot-out over the weekend, while Pirates defeated Stellenbosch 1-0.
Mamelodi Sundowns have a tricky tie on their hands as they make the trip to Port Elizabeth to take on Chippa United, who defeated Bloemfontein Celtic on Tuesday evening.
The other games in the round will see Eric Tinkler's Maritzburg United host MTN8 finalists Highlands Park, while Golden Arrows travel to SuperSport United.
Dates and venues for the clashes will be announced by the Premier Soccer League in due course,
Kaizer Chiefs vs Orlando Pirates
SuperSport United vs Golden Arrows
Chippa United vs Mamelodi Sundowns
Maritzburg United vs Highlands Park