Alfie Potter snatched the winner as Oxford prevented a club record seventh successive League Two defeat.
Damian Batt and Tom Craddock combined on the right, and Potter swivelled to turn in Craddock's cross from eight yards.
Oxford had taken an early lead when Jake Forster-Caskey curled a free kick around the wall from 25 yards. But managerless Wimbledon hit back to lead before the break. First Byron Harrison equalised with a scissors kick from close in, after Yado Mambo's header at a corner came back off the bar.
Then left-back Jim Fenlon unleashed an unstoppable low drive from 30 yards that beat U's keeper Wayne Brown at his left post.
The Oxford goalkeeper was left rooted to his spot early in the second half when Christian Jolley's effort from distance flew over his head but came back off a post. And, nursing an injury, he was replaced soon after.
Deane Smalley made it 2-2 on 55 minutes, following up after Dons keeper Seb Brown failed to hold Sean Rigg's header. Mambo then headed against the bar for a second time and replacement keeper Ryan Clarke pulled off a brilliant save to prove it wasn't Wimbledon's day as Potter came up to sink the visitors.