Mack attended San Marcos High School in Santa Barbara, where he was named the Channel League's Co-Most Valuable Player on defense and earned a first team all-league selection. He was also selected to the All-CIF team. In the classroom, he compiled a 4.2 GPA and a 1180 SAT score.
Mack made 39 consecutive starts for the Golden Bears registering 256 key blocks/knockdowns, 32 touchdown-resulting blocks and 29 down field blocks. Mack compiled a 3.61 undergraduate GPA at the University of California, Berkeley as a legal studies major. He graduated in 2008 and played the 2008 season as a graduate student in education. He won the Draddy Trophy, also dubbed the "academic Heisman", for his academic success in 2008, becoming the first Cal player and the second consecutive center to earn the trophy, following Dallas Griffin of Texas. He also won the Morris Trophy in 2007 and 2008, making him the third offensive lineman and the first since Washington'sLincoln Kennedy in 1991 and 1992 to win the award twice. Mack also represented Cal at the 2009 Senior Bowl.
Mack signed a five-year contract with the Browns on July 25. During the 2009 NFL Season, Mack started on the Browns offensive line every game. After a shaky start, the Browns line, anchored by Mack, paved the way to three consecutive 100+ yard games by Jerome Harrison and one game in which Harrison ran for 286 yards, which stands at third all-time in one game. At the end of the regular season, Mack was selected as center on the All-Rookie team. He started all 16 games, committed only 1 penalty and allowed just 1 sack.
During the 2010 NFL Season Mack again started every game for the Browns. He was named to the 2011 Pro Bowl roster as a second alternate to replace Nick Mangold. In the final minute of the game, he received a lateral and then ran the ball into the end zone for his first career touchdown. During week 5 of the 2011 NFL season, Mack played through appendicitis during a loss to the Tennessee Titans. Mack had an appendectomy during Cleveland's bye week and came back and started against the Oakland Raiders the week after the bye week.