Roy O’Donovan sparked a second-half comeback against MK Dons but the Cobblers were unable to repair earlier damage and bowed out of the Capital One Cup.
The Irish striker opened his account with Town’s goal in a 2-1 defeat in which Ben Reeves and Jason Banton scored for the visitors.
Matt Duke made several superb stops and the Dons might have won by the kind of margin their assuredness in possession deserved.
But O’Donovan’s goal – and the second-half introduction of young trio Ishmel Demontagnac, David Moyo and (especially) Ivan Toney – almost sparked a Northampton revival that looked unlikely for long spells of the game.
Banton produced the first action of the game, cutting in from his left wing and curling a right-footed shot that Matt Duke superbly tipped over the bar.
The save was made by Duke’s footwork – he crucially stepped across to his left before palming the effort to safety.
Duke then showed great relfexes to repel a flicked, low Patrick Bamford volley but the visitors did not have to wait long for their goal.
Reeves was given too much time from 25 yards in which to steady himself and pick a spot just inside Duke’s left-hand post in which to put his shot.
The lead should have been doubled on 27 minutes when left-back Shaun Williams arrived at the back post to meet a cross on the volley but fired his shot straight at the grateful Duke.
O’Donovan had the Sixfields crowd briefly on their feet with a first-time chip after an error by Jon Otsemobor, but while the ball sailed over goalkeeper Ian McLoughlin, it also beat the crossbar.
O’Donovan then forced a strong save from McLoughlin with his left foot, Williams blocking in front of JJ Hooper as he attacked the rebound.
The second half began in open fashion, with Bamford hitting a shot straight at Duke after breaking clean through.
But the ball was in the home side’s net shortly afterwards; Duke, for all his excellent saves, should have held a knee-high shot but instead pushed it back into the traffic and Banton rattled it home.
The defending players in the box also have to take some partial responsibility – they were slow to react to the loose ball, and Banton was not.
Toney, already in the club’s history books as their youngest ever player, was introduced with quarter of an hour to go and immediately gifted a goalscoring chance when McLoughlin scuffed a clearance straight to him.
His strike partner O’Donovan provided the hosts with a lifeline 15 minutes from time when he had the confidence to carry the ball into the box and place a low shot inside McLoughlin’s right-hand post.
Heath should have scored the equalising goal when he headed Demontagnac’s cross wide of the post when in a good position.
Moyo was introduced with five minutes to go and made an instant impression, collecting a superb Demontagnac cross-field pass and driving a shot narrowly wide on the run.
The comeback was alive and well at that point but Duke still had to be alert to keep out a Tom Flanagan header at a corner with an excellent piece of goalkeeping.
A greater margin of victory would probably have been fair on the Dons but credit to the Cobblers, who were indebted to their keeper but made a real game of it in the final quarter.
Cobblers: Duke; Amankwaah, Collins, Heath, Widdowson; Emerton, Deegan, Tozer, Morris; Hooper, O’Donovan
Subs: Demontagnac (for Amankwaah 71), Toney (for Hooper 74), Moyo (for Emerton 86)
Not used: Snedker, Artell, Dias
MK Dons: McLoughlin; Hodson, Flanagan, Otsemobor, Williams; Baldock, Reeves, Gleeson, Banton; Alli; Bamford
Subs: Chadwick (for Alli 61), McLeod (for Bamford 69), Galloway (for Banton 81)
Not used: Martin, Smith, Kay
Away fans: 1,138