The Chairboys dominated the whole game but only had strikes from Kevin Betsy and Tommy Mooney to show for their efforts.
The home side started very brightly, the Oxford goal surviving three attempts in the first two minutes. Betsy had the best of the three chances, having his close range effort deflected for a corner.
The visitors responded well to the early barrage with former Preston hit-man Steve Basham latching onto a knock down by Stuart Gray and firing just wide of the post.
Sergio Torres caused Oxford constant problems, which resulted in three of the visiting players being cautioned in the first period because of his direct running.
The opening goal came on 17 minutes. Clint Easton swung in a corner from the right and following a goalmouth scramble, Betsy smashed the ball into the roof of the net.
The Chairboys continued to make chances. Torres and Mooney forced Billy Turley into saves to keep his sides' deficit to one.
Mike Williamson had a glorious chance after half an hour to double the lead, but he headed over from four yards.
The visitors' goalmouth led a charmed life right at the start of the second period. Mooney somehow allowing Turley to save from a yard and then from the rebound, Torres clipped a lovely shot which hit the post with the keeper beaten.
Wycombe, though, did make their constant pressure pay with the second goal after an hour. Betsy fed the overlapping Danny Senda for his pinpoint cross to be headed in by ex-Oxford striker Mooney.
Oxford halved the deficit with 20 minutes left. A 25-yard free-kick driven in by Lee Mansell was parried by Frank Talia who pushed the ball out for half-time substitute Yemi Odubade to drive the ball into the net.
However, after a few scares, the Blues held on for all three points.