Joel Grant’s penalty wasn’t enough for the Blues as neighbours Oxford secured victory at Adams Park.
The visitors were clinical in front of goal with James Constable, Tom Craddock and John Mullins all on target.
Wycombe struggled to create clear chances and the U’s comfortably held on for the three points.
Gareth Ainsworth made two changes with Jo Kuffour back in after suspension and fit-again Sam Wood making his first start since August. Dean Morgan and Matt McClure were the men to miss out because of slight hamstring complaints.
Oxford started the brighter of the sides and took the lead in the fourth minute when Tom Craddock headed down a long ball and strike partner James Constable drilled home from 10 yards, low to Nikki Bull’s left.
Ainsworth fired a couple of long-range efforts wide as the Blues searched for a foothold in the game, but it was the visitors who looked the liveliest early on and Constable had another strike ruled out for offside.
Wood had the Chairboy’s first effort on goal, but his 25-yard shot was straight at Ryan Clarke and was comfortable for the Oxford keeper.
Substitute Richard Logan, who come on for Kuffour, tried his luck three minutes before the break, but he shot wide from just outside the area.
Wanderers came in close in first-half injury-time when Clarke spilled Charles Dunne’s 25-yard strike, before redeeming himself with a fine save to prevent Joel Grant tapping home the rebound from close-range.
The visitors started the second half as they had the first and doubled their lead within 60 seconds of the restart, Tom Craddock latching on to a ball over the top before expertly firing past Nikki Bull from the edge of the area.
However, the Blues responded immediately and Grant reduced the deficit from the penalty spot, sending Clarke the wrong way, after Dave Winfield had been brought down in the area following a corner.
It was 3-1 in the 62nd minute when John Mullins headed in Sean Rigg’s cross from five yards after Bull had spilled Leven's free-kick.
Grant had a chance to grab the Chairboys a lifeline in the 70th minute, but he fired wide from a difficult angle after neat link-up play involving Junior Morias and Logan found the forward in space in the area.
The game was becoming increasingly stretched and Bull made a great save from Craddock after a fine run and cut-back from Alfie Potter.
Lewis crashed a shot narrowly over from 18 yards and Doherty had an effort turned behind by Clarke as the Blues pushed for a way back into the contest.
Matt Spring had the final chance and he connected well from 20 yards, but his shot drifted wide.