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."
Oxford United 24 McCormick 02 Batt 05 Duberry 06 Wright 16 Whing 26 Davis 27 Davies 09 Constable (Parker - 73' ) 11 Pittman 15 Potter 29 Craddock (Smalley - 52' ) Substitutes 31 Crocombe 23 O'Brien 30 Long 08 Heslop 25 Parker 35 O'Dowda 10 Smalley Wycombe Wanderers 13 Ingram 05 Winfield 18 Dunne Booked 23 Harryman 30 Doherty 08 Lewis Booked 09 Spring 11 Wood Booked 17 Grant 28 Scowen Booked 22 Kuffour Substitutes 21 Harrison 06 Johnson 19 McCoy 07 Ainsworth 12 Andrade 26 Kewley-Graham 32 Morias