UP-Tuks became only the second university after Maties to win the trophy on three occasions.
It was the visitors who started with a bang as lock Janco Venter crashed over for a seven-point try after a few solid phases of play. Flyhalf Chris Smith added the extras to give Maties a 9-0 lead.
UP-Tuks reduced the deficit soon afterwards when flank Chris Massyn barged over for a try, which flyhalf Tinus de Beer converted to make it 9-7 after 10 minutes.
Maties sharpshooters Smith and fullback Tiaan Swanepoel then punished the home team for some ill-discipline as they slotted a penalty each, while De Beer slotted two penalties to make it 15-13 after a gripping first half.
Maties kept the scoreboard ticking early in the second half when Smith split the uprights to increase their lead to 18-13.
UP-Tuks centre Divan Rossouw, however, handed his team the lead when he intercepted a wayward pass to race in untouched for a seven-point try in the 46th minute.
De Beer converted the try and added a penalty minutes later to give the Pretoria students a handy 25-18 buffer with just under 30 minute left to play.
As the teams battled for supremacy, UP-Tuks suffered a setback when replacement prop Jaco Holtzhausen was sinbinned and Maties duly capitalised through the boot of Smith to make it 25-21.
De Beer, however, added a fourth penalty in the 67th minute to restore UP-Tuks’s seven-point lead and the flyhalf then kept Maties pinned in their own half with some excellent tactical kicking.
Maties had a late opportunity to snatch victory but a forward pass ended their attempt and gave UP-Tuks the Varsity Cup trophy.