Luke Beckett's 43rd minute winner was harsh on the Dons who dominated for long spells but could not convert their chances as their barren run in front of goal stretched to four league games.
Dons boss Danny Wilson made three changes to the team that lost 3-0 at Gillingham on Saturday, with Nicky Rizzo and Stephen Quinn restored to the starting line-up at the expense of Gareth Edds and Leon Crooks.
Ben Chorley, back from a three-match suspension, took the place of Pablo Mills after his return to Derby.
Dons started brightly and Izale McLeod sprinted on to Clive Platt's through ball but fired into the side netting from a difficult angle inside the first minute.
Rizzo flashed a 25-yard strike just wide after a mazy run a quarter of an hour in, before Quinn curled a delightful 22-yard effort inches wide of the top corner with goalkeeper Chris Day well beaten.
And as Milton Keynes continued to dominate, Trent McClenahan's cross was clawed into Platt's path six yards out by Day but substitute Rob Scott acrobatically cleared the danger.
Oldham's hopes were dealt a blow just after the half-hour mark when Scott, who had only come on as a sixth minute substitute for the injured Gareth Owen, was himself stretchered off with his neck in a brace.
The unmarked McLeod should have given Dons the lead in the 42nd minute but he shot straight at Day from six yards, before Beckett caught the hosts with a classic sucker-punch a minute later at the other end.
Beckett raced on to Chris Porter's flick from Day's long punt before smashing his fourth goal of the season emphatically past Matt Baker from an acute angle.
Platt and McLeod both had efforts well saved by the inspired Day in first-half stoppage time as the Dons tried to get back on terms, before McClenahan's penalty appeal was waved away minutes after the re-start when he went down under a challenge from Paul Edwards.
McLeod wasted another chance when he stole in unmarked but headed Rizzo's cross wide from six yards in the 65th minute, before Rizzo headed McClenahan's cross inches wide from 10 yards.
The Dons continued to press and Marc Tierney heroically blocked substitute Malvin Kamara's strike from four yards, before Porter wasted a great chance to seal the win for the visitors when he blazed over after McClenahan's error had set him clean through.