University stunned Southern, outscoring its opponent 19-6 in the first quarter to set up the win.
University shooters Kirsten Craig and Lizzie Sandom played well in tandem.
Craig drilled 25 of her 31 attempts and Sandom made 21 of her 24 attempts.
Pip Allen chipped in with five goals from nine attempts.
Southern rallied in the second and third quarters, pruning the gap to 10 goals.
The game was a scrappy affair, with both teams a little tentative.
Southern was missing regular shooter Greir Campbell, who was unavailable due to an injury she sustained in the Lois Muir Challenge.
Coach Georgie Salter opted to play defender Mel Winter in the shooting circle and the move backfired with Winter managing just one goal from three attempts.
Kate Shearer, who landed 28 from 39, replaced Winter at goal shoot in the second quarter and helped her side gain parity.
Southern nibbled away at the lead but was unable to draw close enough to mount a serious challenge.
In the other matches, Phys Ed C posted its second win with a narrow 52-50 victory over Southern B, and Phys Ed A demolished the winless College A 54-28.
With round one complete, College will play premier B leader Macandrew A in a promotion-relegation match on Thursday night.
The winner will earn the right to compete in the premier A grade in the second round.
The men's team had a bye and will drop out of the tournament, after the Dunedin Netball Centre and the clubs decided against allowing the men's team to compete in both rounds.
