Reifers had the top individual score on the par-72, 7,630-yard course just south of Bend, Ore.
The nation's top 30 men's Division I golf teams and six individuals whose teams did not qualify are in the field of 156 players participating in the four-day tournament.
Wake Forest's previous low round was a 278 shot in the fourth round of the 1986 NCAA championship, the last of three national titles for the Demon Deacons.
'It's a tough course if you are not on top of your game,' said Reifers, who had eight birdies and only one bogey. 'It's a long tournament, but we felt it was important to get off to a good start.'
Wake Forest is followed by UCLA at 8-under 280, and top-seeded Oklahoma State and Washington at 7-under. Clemson was fifth with a 282 in the opening round.
Georgia, the defending team champion, was at 5 over. No team has won back-to-back titles since 1984 and 1985 when Steve Elkington and Billy Ray Brown led Houston.
Reifers was followed by Pablo Martin of Oklahoma State, who shot a 6-under 66. USC's Taylor Wood, whose team did not qualify, was also at 6 under.
'He's at a good place right now,' Wake Forest coach Jerry Haas said of Reifers. 'He is striking the ball nicely. I don't have to tell him too much. He has been great to watch.'
Washington's James Lepp, the defending individual champion, was in a pack at 3-under.
The field will be cut to the top 15 teams and the top six individuals not on qualifying teams for Saturday's final round.