Josh Payne struck a brilliant free-kick goal as United bounced back in style from their Macclesfield defeat.
Alfie Potter gave Chris Wilder's men the perfect start with a goal in the fourth minute.
It came after a flowing move, begun by Josh Payne’s incisive pass out to Ben Purkiss on the right wing.
James Constable dummied when Purkiss’s cross came in, and when Tom Craddock played a return pass, Constable crossed low from inside the box, Craddock couldn’t turn it in and it ran loose for Potter to shoot home left-footed from eight yards.
The Cobblers levelled 12 minutes later.
It had not taken time for former Norwich striker Leon McKenzie to look a class act, with his close control, drive and awareness.
And when Liam Davis got free on the left to chip over a dangerous cross, McKenzie rose well at the far post to head home.
The visitors had been threatening, it has to be said, with Michael Jacobs sending a flying header over, Billy McKay drilling a low shot past the far post and Ryan Clarke saving a McKay volley, with which he didn’t properly connect.
Clarke also made a brave punch to clear his lines, and Harry Worley’s crunching tackle on another occasion stopped McKenzie in his tracks.
Having been pressed back before Northampton equalised, the U’s began to regain control after it, and created several good openings.
From a worked free-kick, Simon Heslop’s 20-yard drive deflected narrowly over the bar, and Purkiss fired over on the run, after smart work by Asa Hall and Heslop, spreading play from left to right.
At times the home side were guilty of switching off, the Cobblers taking a short corner easily with no-one challenging, but overall they remained disciplined, and kept their shape.
Anthony Tonkin had a free-kick turned over, but there was nothing goalkeeper Chris Dunn could do when Payne took a free-kick from just outside the box in the 45th minute.
He curled it majestically over the wall and in for his first goal for the club.
Northampton pushed for an equaliser in the second half, but United defended well and played sensibly.
Yet the visitors squandered a glorious opportunity to make it 2-2 with Kevin Thornton sending a close-range shot on the turn wide on 66 minutes.
The game had just entered stoppage time when sub Matt Green slipped a pass to his left to fellow substitute Simon Clist on an Oxford break, and John Johnson barged Clist over, getting a red card for his troubles.
The ref pointed straight to the spot, and Tom Craddock drilled home the penalty to make it 3-1.
Oxford Utd: Clarke, Purkiss, Worley (Creighton 67), Wright, Tonkin, Heslop, Payne, Hall (Clist 83), Potter, Constable (Green 83), Craddock. Subs not used: Batt, Midson, Baker, Eastwood.
Referee: Paul Tierney (Lancashire).
Att: 7,647.
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