Aaron Wilbrahim notched the controversial winner for the home side on 66 minutes, bundling the ball home from a corner, although Cobblers goalkeeper Mark Bunn thought he had kept the ball out.
Cheered on by a massive following of close on 3,000 visiting supporters, it was to prove a massively frustrating afternoon for all concerned with Northampton Town.
Boss Stuart Gray again named an unchanged team as Town targeted a third straight win following the opening day league success over Cheltenham and the midweek Carling Cup win at Millwall.
Have your say on the defeat at MK DonsThe Cobblers dominated the early possession but chances were at a premium, the first coming on nine minutes when Ryan Gilligan won the ball in midfield and had a crack from 25 yards, the ball deflecting off Danny Swailes and dipping just over the bar.
The Dons hit back almost immediately, and Mark Bunn had to be at his sharpest to keep out a close-range header from Wilbrahim, while Mark Wright fizzed a 20-yard shot well wide when he had the time and space to do better.
On 28 minutes the Cobblers had a golden chance to break the deadlock, but top-scorer Adebayo Akinfenwa somehow screwed his left foot shot wide from just six yards out after getting in behind the defence, he should have scored.
Bunn then raced out of his area to brilliantly tackle Sam Baldock as he raced in on goal, it was a perfectly timed effort any defender would have been proud of.
The Cobblers ended the half in the ascendancy and were dominating possession, and it was Akinfenwa who went close again, this time his right foot shot from 15 yards being saved by Willy Gueret.
After a quiet start to the second half, MK Dons upped their game on the hour mark and should have taken the lead, but Florian Sturm headed wide from six yards when it looked easier to score.
Jackman saw a long-range shot saved by Gueret before the home side did break the deadlock in scrappy and controversial fashion on 66 minutes.
Wilbrahim was the man credited with the goal after a scramble in the box, but Bunn clearly felt he had stopped the ball from crossing the line – the assistant referee didn't agree and flagged for the goal.
Bunn saved well from the veteran Kevin Gallen as the home side went for the kill, while the Cobblers threw on Giles Coke and Colin Larkin into fray as they strived for an equaliser, and it so nearly came two minutes into stoppage time.
Larkin broke through the middle and played in Akinfenwa, the big man waited for Gueret to come off his line and tried to dink the ball over him, but he didn't get enough height on the shot and the ball thudded into the goalkeeper's chest.
But that was as close as Town would come as the game ended in disappointment and anti-climax for the Cobblers and their massive support.
Teams: MK Dons: Gueret, Lewington, Swailes (71m, Stirling), O'Hanlon, Leven, Wright, Navarro, Sturm (62m, Cummings), Regan, Baldock (62m, Gallen), Wilbrahim. Subs not used: Abbey, Johnson. Northampton: Bunn, Crowe, Jackman, Hughes, Gyepes, Doig (73m, Coke), Constantine, Akinfenwa, Davis, Gilligan (82m, Larkin), Guttridge (55m, Osman). Subs not used: Holt, Dunn.
Referee: Gavin Ward. Attendance: 12,078
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