Josh Morris struck late on to earn Scunthorpe a 1-0 victory that ended Oxford's 100 per cent start to the season.
The winger netted in the 83rd minute when his ball in from the right ran through the penalty area and nestled into the far corner.
It was the first Sky Bet League One goal the U's have conceded this season, but it came on the back of a strong spell of home pressure.
In a tight first-half chances were few and far between, with the visitors creating the only real opening when Matt Gilks tipped a Jack Payne header onto the bar.
After the break, the Iron got on top and Oxford lived dangerously before conceding.
Tom Hopper should have headed the hosts ahead following a cross from Paddy Madden and Neal Bishop later floated an effort onto the bar.
When Madden saw a deflected shot drop wide after bouncing up over keeper Simon Eastwood, it looked like it might not be the home side's day.
But Morris struck and they held out for the win, despite Jon Obika hitting the bar in stoppage time.