McCullers committed to Tennessee in January 2012, in part because the team was transitioning to a 3-4 defense, with which McCullers was more familiar with. He finished the 2012 season with 39 tackles (20 solo), including a sack and 5.5 tackles-for-loss, to go along with a forced fumble and a pass broken-up. He recorded eight tackles and blocked a PAT in Tennessee's loss against Georgia, and registered eight tackles in the Vols' loss to South Carolina.
After Tennessee head coach Derek Dooley was fired late in the 2012 season, there was speculation that McCullers would forgo his final year of eligibility and enter the NFL Draft. He decided to return for his senior year, however, even though the Vols' new head coach, Butch Jones, was planning to install a 4-3 defense. Recognizing the importance of McCullers making a successful transition to the new scheme, Jones stated prior to the 2013 season, "We'll be as good as Dan McCullers goes." He was named to the Athlon Sports Preseason Third Team All-SEC, and Phil Steele's Preseason Fourth Team All-American and Preseason First Team All-SEC. He finished the season with 33 tackles (21 solo), including 4.5 tackles-for-loss. He recorded six tackles in Tennessee's upset of South Carolina, including a sack that knocked quarterback Connor Shaw out of the game. He also blocked the second PAT of his career in the Vols' loss to Auburn. He appeared in the 2014 Senior Bowl.
While at Tennessee, McCullers received frequent attention for his enormous size. He was the subject of a USA Today feature in September 2012, and a photograph of McCullers towering over a Tennessee trainer was widely circulated on the web. He acquired numerous nicknames, such as "Mount McCullers", "Shade Tree" McCullers, "Big Dan," "Green Mile,"—after Michael Clarke Duncan's role in the 1999 film The Green Mile— and "Man Mountain."