Venter was given a lifeline in Durban after his English club, Worcester Warriors, was put under administration recently, and will add some valuable experience to the Cell C Sharks' midfield.
With their core Springboks not available for selection this week, the KwaZulu-Natalians have nonetheless named a powerful squad for the match.
As a result, there are a number of changes from the team named for last weekend's match against Ulster, which was called off a day before kick-off.
Upfront, Gerbrandt Grobler replaces Springbok lock Eben Etzebeth in the second row from their match a fortnight ago against the Glasgow Warriors, while Venter's inclusion is one of three changes to the backline.
Cameron Wright takes over from Springbok scrumhalf Jaden Hendrikse and Thaakir Abrahams is in for Anthony Volmink.
Venter, capped seven times for the Boks, gets his debut start ahead of Marnus Potgieter, who has been named on the bench.
Aphelele Fassi, Phepsi Buthelezi, Thomas du Toit, Ntuthuko Mchunu, Sikhumbuzo Notshe and Grant Williams, all of whom were named in the Springbok and South Africa 'A' squads on Friday morning, will play in Pretoria before moving across to national duty.
The match at Loftus Versfeld kicks off at 15h00 on Sunday and will be broadcast live on SuperSport.
Cell C Sharks: 15 Aphelele Fassi, 14 Werner Kok, 13 Francois Venter, 12 Ben Tapuai, 11 Thaakir Abrahams, 10 Boeta Chamberlain, 9 Cameron Wright, 8 Phepsi Buthelezi, 7 Vincent Tshituka, 6 Dylan Richardson, 5 Hyron Andrews, 4 Gerbrandt Grobler, 3 Thomas du Toit (captain), 2 Kerron van Vuuren, 1 Ntuthuko Mchunu. Replacements: 16 Dan Jooste, 17 Dian Bleuler, 18 Carlu Sadie, 19 Justin Basson, 20 James Venter, 21 Sikhumbuzo Notshe, 22 Grant Williams, 23 Marnus Potgieter.