MK Dons survived the sending off of Shaun Cummings to make it nine league games without a victory for Orient.
Luke Chadwick played a one-two with Peter Leven to open the scoring for MK Dons after 19 minutes, then turned in Mark Wright's cross four minutes later.
Adam Boyd missed a penalty for Orient five minutes after the interval following Cummings' red card for a foul on Sean Thornton.
Tamika Mkandawire turned in Orient's consolation goal in injury time.
Leyton Orient: Morris, Purches, Thelwell, Mkandawire, Granville, Morgan (Melligan 46), Chambers, Terry (Thornton 46), Demetriou, Boyd (Jarvis 72), Parkin. Subs Not Used: Jones, Saah.
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