Bettinger (3-5, 5.43 ERA) gave up a run in a shaky first inning, but settled down afterward, with a final line of two earned runs on six hits, with four strikeouts and one walk, on 103 pitches.
Virginia (38-20), the top seed in the regional and the defending national champion, took the lead for good with a pair of two-out RBI hits in the second inning, by Jack Gerstenmaier and Cameron Simmons.
The Cavs added three in the third, on an RBI single by Pavin Smith and a two-run double by Charlie Cody, before salting the game away with a three-run fourth, on a two-run homer by Ernie Clement and an RBI single by Matt Thaiss.
UVA posted 20 hits on the day, a program record for an NCAA Tournament game.
Dan Powers (8-6, 4.42 ERA) took the loss for William & Mary (29-30), giving up six runs on seven hits in three-plus innings.
The ‘Hoos advance to the winners bracket Saturday to face the winner of Friday’s second game between Bryant (47-10) and East Carolina (34-24).