The team from Port Elizabeth will have a tough task on their hands when they take to the pitch at the Fanie du Toit Sports Grounds for their fourth consecutive away game.
Madibaz head coach Graeme Harrison said NMMU's position at the bottom of the log left the team no choice but to go for a clear win to stay in the competition.
"We have to give ourselves a chance against NWU-Pukke. They are a good team and it's going to be very difficult to beat them, especially in their own backyard," said Harrison.
"But we are going there determined to come home with the three points."
Pukke are fourth in the standings after three rounds and will be looking to remain in contention for a semifinal spot.
"We know it's going to be a high tempo, fast-paced game, so we have been preparing for that," said Harrison.
"Preparation has been going well and the players have been hard at work."
Making his Varsity Football debut on Thursday will be young Chuma Mapuma, who gets his start ahead of regular Sachin Jackson.
"He is a young prospect with huge potential and we hope he'll make an impact on the game," said Harrison.
In the only other change, Diego van Rooyen replaces midfielder Litha Fingo, who will start on the bench.
"Van Rooyen is an exciting player who also has a lot to offer to the team. I am expecting a good performance from him," said Harrison.
The match kicks off at 6.30pm.
NMMU Madibaz: 1 Matthew Booysen, 2 Onela Beqezi, 3 Lonwabo Balfour, 16 Lundi Balfour, 5 Athini Bisha, 4 Diego van Rooyen, 20 Zusakhe Sali, 8 Fuzo Zantsi, 9 Chuma Mapuma, 10 Cloudius Sagandira, 18 Simamkhele Thobi. Substitutes: 25 Xola Fipaza, 19 Onke Matomela, 6 Ekow Anfoh Assan, 17 Achuma Klaas, 7 Sachin Jackson, 15 Litha Fingo, 12 Lusapho Mlangane.