Wake Forest (36-6, 15-3 ACC) took its first lead in the eighth inning on Jeff Ruziecki's two-run homer off Tiger reliever Paul Harrelson who took the loss.
Kyle Sleeth kept his perfect record intact, improving his record to 9-0. Sleeth went seven innings, giving up just one earned run on six hits with six strikeouts. It was the fourth nationally-ranked team Sleeth has defeated this season.
Dave Bush fired two innings of scoreless relief for his 10th save of the year.
Clemson (33-6, 10-3 ACC) took a 2-0 lead into the eighth inning on the strength of starter Steve Reba. But the Deacons got to the Wake Forest bullpen in the eighth. Nick Blue led off with a double and later scored on a sacrifice fly by Jamie D'Antona. Steve LeFaivre singled and Ruziecki blasted a 2-1 pitch over the wall in right-center field. For Ruziecki, Cypress Junior College's all-time leading home run hitter, it was his first home run since March 1 against Appalachian State.
Clemson loaded the bases in the ninth but Bush struck out Russell Triplett looking to end the game.
It extended Ruziecki's hitting streak to 12 games which also equals the current Demon Deacon winning streak. That streak ties for the second longest in school history.
Blue and Ryder Mathias each had two hits. D'Antona and Ruziecki drove in two runs.
The Deacons go up 2.5 games ahead of Clemson in the ACC standing and improve to 5-1 against opponents ranked the top five this season. Wake Forest and Clemson will continue their weekend series on Saturday at 7:00 p.m. The game will be televised on Fox Sports South. Junior Seth Hill gets the start for the Deacons.