A superb individual goal from Joel Grant gave Wycombe victory at Oxford.
Former Crewe winger Grant beat two defenders and fired past Luke McCormick for his 10th goal of the season.
The hosts wasted a number of chances to equalise, Tom Craddock missing the best when he headed Jon-Paul Pittman's cross over the bar from four yards.
Pittman hit the post with an angled shot shortly afterwards as Oxford's winless run in League Two was extended to five matches.
VIEWS FROM THE DRESSING ROOM
Wycombe Wanderers player-manager Gareth Ainsworth told BBC Three Counties Radio:
"The goal was sensational from Joel Grant - absolutely sensational - it was good enough to win any game.
"The fans, the players and everyone connected with Wycombe should be really proud today because it's a really good target reached.
"We're probably safe now, and looking up, people are starting to talk about the playoffs, which is crazy.
"We've still got five games and it's great for us to have these games and have a say in what happens in the league."