The Cod Army had to play with a man short for 84 minutes after losing experienced centre-half Charlie Mulgrew to a straight red card in only the sixth minute.
Josh Ruffels headed home from a corner in the 29th minute as Oxford made it eight successive wins to equal a club record, and leave interim manager Simon Wiles still looking for his first victory six games after replacing Joey Barton.
The misfiring Cod Army, with only one goal from Wiles’ five league games in charge, are now nine points off the play-off places and hold the same gap over the relegation places
Mulgrew went for his early bath for a professional foul on Matty Taylor as the striker bore down on goal.
Town started with January signings Kyle Vassell and Janoi Donacien in the starting line-up , and with Nathan Sheron on the bench following his recall from St Mirren.
Vassell, who had spent some time with Oxford in a loan spell six years ago, almost got on the end of a through-ball in the opening few minutes, just beaten to it by keeper Jack Stevens.
But the visitors’ bright start suddenly became a nightmare as Mulgrew brought down Taylor when the in-form striker darted in behind him from Sam Long’s pass. The defender was immediately shown the red card by referee Sam Barrott.
It was possibly harsh in that there was also another defender alongside Mulgrew, but it did look a cynical challenge.
Two minutes earlier, Taylor had seen a goal disallowed when he thought he had stayed onside, only to be denied by a linesman’s flag in what looked a very tight decision.
Mulgrew’s foul was at least outside the box, though, and Town defended the free-kick well.
Wiles made the decision to sacrifice Harvey Saunders so he could bring on defender Harrison Holgate and plug the gap left by Mulgrew.
It inevitably became mainly one-way traffic from then on, and Alex Cairns made a good save from James Henry’s angled shot on 18 minutes.
But the home side broke the deadlock just before the half-hour mark and it came from a set-piece.
Elliott Moore headed Henry’s corner forward and Ruffels nodded the ball home from close range.
As Oxford continued to press, Callum Connolly made an excellent brave block to prevent it becoming 2-0.
The second half continued with Oxford having nearly all of the ball and Vassell often a lone figure up front for Town, sometimes with captain Paddy Madden in support.
Cameron Brannagan went close to extending the lead with a left-footed drive from 30 yards that hit the top of the bar.
There had not been many opportunities for Wiles’ men to threaten but they did near the hour mark when they won a corner.
Connolly headed forward and from six yards out Holgate almost turned the ball in, Stevens saving with his foot.
Oxford made a triple substitution to liven their team and two of them combined on 65 minutes.
Sam Winnall struck a shot against the post and his fellow sub Dan Agyei should have scored from the follow-up but he delayed too long, allowing defenders to block.
Fleetwood, still believing they could snatch an equaliser, had moments near the end, but couldn’t test Stevens again, and they were left to rue the mountain they had to climb after Mulgrew’s early dismissal.
Oxford: Stevens, Long, Moore, Atkinson, Ruffels, Brannagan, Gorrin (Hanson 64), Kelly (Winnall 64), Henry, Taylor (Forde 85), Shodipo (Agyei 64); Subs not used: Eastwood, Hall, Sykes.
Fleetwood: Cairns, Donacien, Connolly, Mulgrew, Andrew, Rossiter, Camps, Duffy (McKay 77), Saunders (Holgate 10), Vassell (Garner 78), Madden; Subs not used: Coleman, Morris, Sheron, Rydel.
Referee: Samuel Barrott
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