Wake Forest slipped to 36-7 overall, 15-4 in the ACC but remains in first place in the conference. Sunday's game will determine the leader in the race for the regular season title.
Seth Hill took his first loss, dropping to 3-1. He pitched 5.1 innings, giving up five runs on seven hits with a pair of strikeouts. Daniel Davidson, Ryan Lewis and Adam Hanson combined for 2.2 innings of scoreless relief but the Deacons could not muster another late-game rally.
Clemson's B.J. LaMura earned credit for the win while Patrick Hogan got his third save.
The Deacons were outhit for just the 12th time this season but had their opportunities. Wake Forest stranded 11 runners, seven of those in scoring position.
The Tigers got on the scoreboard with a run in the first inning and pulled out to a 4-0 lead after three runs in the fourth.
In the sixth, the Deacons crawled back into the game with two runs on RBI singles by Jeff Ruziecki and Adam Bourassa. Stephen Ghutzman's solo homer in the seventh made it a 5-3 game but the Deacons would get no closer.
Freshman shortstop Ben Ingold went 2-for-2 at the plate with a double.
The Deacons and Tigers will conclude their weekend series at 2:00 p.m. on Sunday afternoon at Kingsmore Stadium in Clemson, S.C. Junior Ryan Braun will make his third start.