The reigning ACC Pitcher of the Year allowed five hits in 6 2/3 innings of shutout work, during which Clemson stranded eight runners.
A total of 10 were left on base.
"You know it's going to be a close ball game, coming in," said Clemson coach Jack Leggett, "so any run you can pick up is a necessity."
The shutout snapped Clemson's streak of 147 games with a run. The previous shutout was on May 22, 2008, a 10-0 ACC Tournament loss to N.C. State.
Chris Epps, who led off the first inning with a double, was the only Tiger base runner to advance past second base.
"We had a couple of opportunities early in the ball game to establish ourselves and put a little pressure on him and we didn't do anything with it," Leggett said.
The loss dropped Clemson to 7-4 overall (0-1 ACC). Virginia improved to 14-1 (1-0 ACC).
In 6 2/3 innings, right-hander Scott Weismann gave up eight hits, five runs, three of which were unearned.
Leggett said Weismann threw well enough to keep the Tigers in the game.
"I made a little adjustment during the week, staying back a little more," Weismann said. "I felt like I get better command, and I felt my off speed was a little bit better tonight."
Virginia touched him up for a run in the third when John Hicks drove in John Barr on a single.
Hultzen, the Cavaliers' cleanup hitter, who is also a Golden Spikes watch list member, platted the second run with a sixth inning sacrifice fly to leftfield.
Virginia tacked on three more with a two-out rally an inning later.
Chris Taylor singled in David Coleman before scoring on a Brad Miller error. Hultzen kept the rally alive with a RBI single up the middle. Freshman right-hander Kevin Phole was on the mound in relief when the Cavaliers' fourth and fifth runs crossed the plate.
Hultzen was one of two Virginia base runners caught trying to steal second by Spencer Kieboom, who also threw out Steven Proscia to end the sixth inning. The Clemson catcher also went 1-for-3 from the plate.
Jeff Schaus was the only Tiger batter with multiple hits (2-for-3). Epps and Will Lamb were the only others to reach base more than once.
As a team, Clemson struck out 18 times. Justin Thompson had four in his 2 1/3 innings of relief for Hultzen.
"We struck out a little too many times. When you strike out that much, you're going to have trouble winning the ball game," Leggett said.
Tiger right-hander Dominic Leone, who made his second-straight appearance, struck out two batters in the eighth. Righty Justin Sarratt also had a scoreless inning of work.
"We've got to put this one behind us and we've got a good opportunity. We've got two more games ahead of us," Weismann said. "We've got to flush this one. We can still win the series, so we'll come out ready to play tomorrow and Sunday, for sure."
The two teams meet again at 2 p.m. on Saturday and 1 p.m. on Sunday.
Tigers held scoreless in ACC opener
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