Jabo Ibehre and Dean Bowditch scored as MK Dons made Exeter pay for their lack of cutting edge with an away win.
Ibehre capitalised on some sloppy Exeter defending to lash home a loose ball from 12 yards.
Nicholas Bignall headed Exeter's best chance wide from six yards out on the stroke of half-time and they lacked an end product again after the break.
Bowditch made them pay in the final minute, beating the offside trap and slipping the ball under Artur Krysiak.
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Exeter boss Paul Tisdale told BBC Radio Devon:
"No excuses for the result and no real issues with the game either.
"The players worked very hard and we just have to pick ourselves up.
"The way we were set up today, to break them down with the lack of firepower we had was always going to be difficult."
MK Dons boss Karl Robinson told BBC Three Counties Radio:
"I felt we showed a different side to our quality today. A little bit of grit and determination, a little bit of heart and passion.
"There were some outstanding performances, there were some not so good ones. But the ones that didn't play well, the rest got them out of trouble and that is most important.
"We knew they would have a go at us early on. I don't think they created many chances to be fair. We denied them opportunities, but they had an awful lot of possession."