The Cobblers conceded twice in two costly first-half minutes to suffer their first defeat in three matches, against Oxford United.
James Constable’s strike and Danny Rose’s penalty came in the final minute of the first period of play at the Kassam Stadium and effectively ended the contest.
Town failed to score for the sixth time in 11 league games this season as the hosts closed out an almost entirely uneventful second half and a 2-0 win.
The defeat means Northampton have now failed to win at the Kassam Stadium for seven years and ensures they remain the Sky Bet League Two relegation zone.
Injuries to Joe Widdowson and Chris Hackett forced the Cobblers to make two changes to the side that won at Wimbledon, with Ben Tozer and Stuart Dallas drafted in as direct replacements.
Roy O’Donovan, who was a doubt for the game with a slight ankle injury, recovered from that and made a good start to proceedings, cutting off a weak Michael Raynes back pass and forcing an early corner that ended with a Gary Deegan shot into the car park.
It was right-back Kevin Amankwaah who unexpectedly got into the first good scoring position of the game, Deegan flicking a pass inside Tom Newey for the defender to run onto and bear down on goal.
Ryan Clarke left his line to limit the angle and the finish was ultimately lacking in both composure and direction, flying wide of the target at the near post.
Town then had to withstand something of an Oxford barrage; first Matt Duke parried an Andy Whing shot from the edge of the box and then Paul Reid blocked a Sean Rigg shot from almost point-blank range.
Darren Carter almost found the target with a scorching volley from 25 yards, chesting a bouncing ball down and then hitting the ball beyond Clarke with the outside of his foot but also beyond the post by a matter of inches.
On the stroke of half-time, though, Constable broke the deadlock, collecting a pass in the inside-right channel and forcing Reid onto the back foot in his own area.
Reid slipped at the crucial moment, providing just enough space for a shot which Constable rapped underneath Duke from 10 yards.
And things went from bad to worse seconds when Constable, again finding space down the right, went to ground under a challenge from Tozer when contact appeared minimal, referee Darren Deadman pointing immediately to the spot.
Danny Rose drilled home the penalty to completely alter the complexion of a game that was even for its first 44 minutes.
The two-goal cushion allowed Oxford the security to stand off their opponents and let them have the majority of the ball in the second half but that was a dangerous policy, as substitute Ivan Toney had two early attempts blocked, the first from almost on the goal line.
The contest became a virtual non-event midway through the second half, with the Cobblers working hard - in vain - to create openings and the hosts putting the emphasis firmly on defending.
It was, therefore, no surprise at all, that no goals were added to the scoreline.
Oxford: Clarke, Hunt, Wright, Raynes, Newey, Mullins, Rose, Whing, Rigg, Kitson, Constable
Subs: Williams (for Rigg 76)
Not used: Smalley, Hall, Davies, Crocombe, Bevans, Ruffels
Cobblers: Duke, Amankwaah, Reid, Doumbe, Tozer, Dallas, Collins, Carter, Deegan, Morris, O’Donovan
Subs: Toney (for Collins 46), Hooper (for O’Donovan 68), Emerton (for Morris 71)
Not used: Demontagnac, McNamara, Harriott, Dias
Away fans: 910
Referee: Darren Deadman