On-loan Watford forward Jerome Sinclair scored his first goals for Oxford to see off Scunthorpe and earn a vital three points in their bid to beat the drop from League One.
Substitute George Thomas pulled one back for the visitors in stoppage time but could not prevent the U's notching back-to-back league wins for the first time this season.
Scunthorpe were quickly out of the blocks with Funso Ojo having a low shot saved in the first minute.
But that was as good as it got in a drab first half, with the home side's best opportunity squandered by a heavy touch from Mark Sykes when Sinclair played him through.
After the break Scunthorpe's Olufela Olomola sent an 18-yard drive fizzing past the far post.
But Oxford had more attacking zip when Gavin Whyte came off the bench and Sinclair took full advantage, first heading in a left-wing cross from Sykes in the 65th minute.
He escaped his marker again to head home John Mousinho's classy cross in the 80th minute, before Thomas turned in Tom Pearce's centre late on.
Oxford climb a place to 19th in the table but remain two points above the bottom four after Bristol Rovers won.
Report supplied by the Press Association.