Bryant, a sophomore from Brooklyn, N.Y., started 31 of the team's 35 games this season, averaging 9.3 points, 3.1 assists and 2.2 rebounds. The No. 2-seeded Mountaineers play No. 11-seeded Washington Huskies in Thursday night's East Regional semifinals at the Carrier Dome in Syracuse, N.Y.
School officials said Bryant fractured the fifth metatarsal in his right foot.
Bryant will probably be replaced in the starting lineup by junior Joe Mazzulla, whose playing time has increased recently after he missed most of last season with a shoulder injury. Mazzulla is averaging 2.2 points and 1.8 rebounds, but he had 15 assists in the last three games.
"It hurts our depth a little bit," West Virginia coach Bob Huggins told ESPN.com's Dana O'Neil on Tuesday night. "But Joe is ready. He's been playing really well for us. He shot the ball really well in practice and in the games. He'll be fine."
Mazzulla's last start came against Davidson on Dec. 9, 2008. He hurt his right shoulder in that game, missed the rest of the season and had surgery. His shoulder limited his shooting mobility for much of this season.
The Mountaineers have no other point guards on their roster but have used forwards Da'Sean Butler and Devin Ebanks in stretches at the position. Earlier this season, West Virginia used an all-forward starting lineup in four straight games, going 3-1.
Huggins said he isn't sure if Bryant broke his foot in practice or during last week's NCAA tournament games. Huggins said Bryant complained that the foot hurt during practice, so X-rays were taken on Tuesday.
"Everyone is good," Huggins said when asked how his team responded to Bryant's season-ending injury. "They're sad for Truck, obviously, but they're fine."
Bryant's injury couldn't come at a worse time for West Virginia. Washington is led by point guard Isaiah Thomas, who is averaging 17.1 points and 3.1 assists.
Mazzulla, from Johnston, R.I., has seen increased playing time during the NCAA tournament. In the Mountaineers' 77-50 win over No. 15-seeded Morgan State Bears in the first round in Buffalo, N.Y., Bryant scored four points with three assists in 22 minutes and Mazzulla had five points with six assists in 22 minutes.
In West Virginia's 68-59 second-round victory over the No. 10-seeded Missouri Tigers, Bryant had four points with one assist in 16 minutes and Mazzulla scored three points with two assists in 24 minutes.
Mark Schlabach covers college football and men's college basketball for ESPN.com. Information from ESPN.com's Dana O'Neil and The Associated Press was used in this report.