Goals in each half by Ryan Crowther and Junior Brown made it four games unbeaten for the Cod Army, who had thrashed the U's 3-0 at Highbury Stadium less than three weeks ago.
Crowther finished well on 28 minutes at the Kassam Stadium after Conor McLaughlin and David Ball played it quickly across the area from right to left, leaving Oxford's defenders outnumbered.
And, ten minutes into the second half, Junior Brown nipped into the six-yard box to make it 2-0 with a low diving header.
Jean-Michel Fontaine should have made it three, but stabbed his shot wide.
The U's, lacking in confidence, were very shot-shy, with Alfie Potter electing to pass rather than pull the trigger in front of goal.
Potter did have a header cleared off the line in the second half, though, when James Constable also struck a post with a left-footed drive.
Liam Davis pulled a goal back for Oxford in the 89th minute with a brilliant 20-yard shot, but it came too late.
Chris Wilder's team have now picked up just one point from the last five games.