Jessica McCreery, Emma Hennessy and Lydia Shelton scored the tries for Swansea with Cardiff’s only score coming from flanker Eve Jones.
Thousands of students turned out to watch the historic fixture at the home of Welsh rugby.
The girls in red took victory at last year’s Welsh Varsity, running out 19-18 winners at a packed Sketty Lane in Swansea.
But in the last outing between the two sides, Swansea bagged a last-minute try to steal the game from Cardiff with a 14-12 in their BUCS fixture.
Swansea – coached by Wales Women’s international Siwan Lillicrap – came out of the blocks firing and raced into an early lead with full-back Megan Griffiths holding her nerve with a penalty in front of the posts.
Minutes later it got even better for the visitors when scrum-half McCreery scored off the back of a driving maul, making Welsh Varsity history in the process – the first woman to score a try at Principality Stadium in the competition.
Cardiff responded positively and could count themselves unlucky not to get a try on the board before the break.
And Swansea made the hosts pay for missed opportunities when rapid wing Hennessy waltzed her way through unscathed just minutes prior to half time.
A fired-up Cardiff team – guided by Richard Jones in is eighth year at the helm – got themselves on the scoreboard in the 42nd minute.
Patient play from the forwards eventually led to Jones bruising her way over in the corner.
Cardiff lost Jenny Benton to the sin bin for not rolling away at the ruck and Swansea capitalised on the extra player with No 8 Lydia Shelton crashing over.
Claire Morgan’s inside break gave Cardiff ground and that pressure led to Courtney Keight being shown yellow for a high tackle.
But Cardiff – for all their patience and possession – were downed by not finishing or making the most of their chances as Swansea held on for the victory.