Talib Zanna had 17 points and nine rebounds and Josh Newkirk added 10 points and five assists off the bench for the Panthers (24-8), who face fourth-seeded North Carolina in Friday's quarterfinals.
Coron Williams scored 16 points and Codi Miller-McIntyre had 10 for the Demon Deacons (17-16), who alternated wins and losses over their last six games.
Pitt jumped out to an 11-2 lead in the first 3:40 of the game before using a 10-5 run later on to stretch its lead to 21-9. An exchange of scores through the final 10 minutes left Wake Forest trailing 39-25 at the half.
Wake Forest came as close as 13 points down, 43-30, with 17:44 left before the Panthers ran away with the game over the remainder of the contest.