Tom Craddock, who scored four last weekend at Accrington, set up the first for James Constable who opened his account for the season.
And Craddock then smashed a long ball past Bull less than a minute into the second half.
The Wycombe response was instant with Constable fouling player-manager Gareth Ainsworth in the box and Grant tucking the penalty home.
Johnny Mullins snuffed out the revival though when he headed home Sean Rigg's cross on 62 minutes.
It was Oxford's first league win at Wycombe since 2005 and means Wycombe have only won two of their last 11 home games.
