He is a native of Mississippi and played collegiately in that state for Alcorn State University, a historically black university which competes in the NCAA's Division I-AA. In his senior season he amassed incredible statistics, including over 4,000 yards passing and 2,000 yards rushing; he finished third in the voting for the Heisman Trophy, which is unusual for a player from Division I-AA. His brother Fred also played for Alcorn (from 1986-1989), later playing 10 years in the AFL. Steve was subsequently selected with the third pick in the ensuing NFL draft by the then-Houston Oilers, who were in the process of relocating to Tennessee. McNair was brought along slowly in the NFL by the Oilers, backing up or sharing time with quarterbacks Chris Chandler and Dave Krieg.

When the team relocated to its new stadium in Nashville and was renamed the Titans in 1999, McNair, along with running back Eddie George, led the team to an AFC championship and an appearance in Super Bowl XXXIV, where they lost by only a yard to the St. Louis Rams. Since then, he has generally been recognized as one of the game's top players, and was named co-Most Valuable Player for the 2003 season along with Peyton Manning of the Indianapolis Colts.

McNair was widely respected among Titans fans for being able to play while hurt, having sustained many injuries throughout his career. In the 2003 and 2004 seasons, however, he was increasingly forced to take time off due to injury, being replaced by adequate backup Billy Volek. On November 28, 2004, after a loss to the Houston Texans, McNair hinted that he might retire following the 2004 campaign. On December 17, 2004, it was announced that McNair would not play any more during the 2004-05 season and that he would undergo surgery on his injured sternum. McNair's return for the 2005 season, however, was a stellar display of his co-MVP-winning 2003 season form.