The Cobblers needed just a point in their derby with MK Dons but a solitary first-half goal from Aaron Wilbraham denied them and now they face a difficult trip to Leeds.
Northampton failed to get going in the first half and it was MK Dons who created the better chances as they took hold of the game early on.
Sam Baldock fired wide of an open goal from the rebound when Chris Dunn couldn't hold on to a Carl Regan shot, Jason Crowe clearing off the line from Mark Wright as the visitors created chances at will.
They finally broke the deadlock in the 34th minute when Jason Puncheon raced down the left and his low cross was turned in by Wilbraham.
Wright almost added a second in the 41st minute from Wilbraham's cross but Luke Guttridge should have equalised two minutes later when he fired over from close range.
Northampton threw on a less than fully-fit Adebayo Akinfenwa at the start of the second half in a bid to get back into the game. But Baldock missed another good chance for the Dons when he allowed Dunn to save after he was picked out by Wright's low cross.
Northampton gradually created some chances of their own. Guttridge saw his goalbound shot blocked and substitute Leon Constantine could only put the rebound into the side-netting.
Substitute Adam Watts twice went close, heading wide from Danny Jackman's corner and then having another effort cleared off the line by substitute Luke Chadwick. Keeper Dunn came up for another corner in stoppage time but could only head over.