Despite missing half their team through injuries and international call-ups, they were always the stronger and more adventurous outfit. And they capped an excellent team performance with three classy goals.
Lee McEvilly notched a brace to take his tally to four in the last three games, before Mark Jones hit a stunning third with an angled 25-yard drive into the left corner of the goal.
Jon Walters pounced on a slip by Chris Willmott to set up McEvilly for his first goal in the 39th minute.
McEvilly got his second with a far-post header from Darren Ferguson's corner on 58 minutes after Willmott failed to stay with his man.
U's boss Brian Talbot was furious with his team's lacklustre display in the first 45 minutes and made three changes at half-time.
One of his subs, Craig Davies, felt aggrieved when he had a goal ruled out for offside and it looked a very tight decision.
Jones wrapped up Wrexham's victory with a fantastic shot from Matt Crowell's pass.
It was Oxford's heaviest home defeat since they moved to the Kassam Stadium four years ago.