The Patriots (22-5, 14-2) won their 12th in a row, while the Rams (20-8, 12-4) lost back-to-back games for the first time this season.
Cam Long added 14 points and Vertrail Vaughns had 12 for George Mason, which took command of the game after allowing the Rams to score the first basket. The Patriots reeled off the next 11 points and never looked back.
Mike Morrison and Luke Hancock each added 10 points for George Mason, and Hancock's came on 10-of-10 shooting from the free-throw line.
Virginia Commonwealth, which sputtered to only 19 first-half points, shot 37 percent from the field (20 of 54) and never found its rhythm. Rob Brandenberg was the only Ram in double figures with 12 points.