Nicky Wroe struck with three minutes remaining to eventually break the resistance of 10-man Wycombe and earn Oxford a first win in six.
Wanderers were left facing an uphill task when Steven Craig was sent off for violent conduct with just 20 minutes of the match gone.
Yet the Chairboys held out for most of the game and could have won it through Gary Doherty only for Wroe to fire in at the close.
Craig initially escaped any action from referee Brendan Malone after appearing to lean his head into Oxford defender Michael Raynes' face.
However, the 32-year-old striker was soon sent off after it was judged he had led with his elbow in an aerial challenge on Johnny Mullins.
Oxford pressed hard after the break as first Wroe hit a long-range shot wide and James Constable and Ryan Williams both fired over.
Yet Wycombe had a great chance to win it when Doherty's shot was blocked by the legs of U's goalkeeper Ryan Clarke.
However, it was Oxford who won it with time running out when Wroe received the ball just outside the area and crashed a shot into the far corner.