Tweety Knight and Kerry Hammonds added 11 points apiece for third-seed Middle Tennessee (24-8). Shawn Jones grabbed 11 boards for the Blue Raiders, who move on to the semifinals against Tulsa.
Ambrose Mosley scored 13 points for sixth-seed Old Dominion (16-17), which also got 12 points from Richard Ross and 10 from Keenan Palmore.
Middle Tennessee ran out to a 30-19 lead at halftime after shooting an even 50 percent from the floor in the first half. Old Dominion couldn't keep up, connecting on only 27.6 percent.
The Blue Raiders were even better in the second half, as they coasted to victory on the back of a 60 percent shooting effort.
Middle Tennessee outscored the Monarchs 30-10 in the paint.