After graduating from BYU in 1981, Reid spent one year as a graduate assistant on the school's football coaching staff. He spent the next nine years as an offensive line coach with four different colleges.  He was hired as an assistant coach by the Green Bay Packers in 1992, the same year quarterback Brett Favre became a member of that team. Reid was named the Packers' quarterbacks coach in 1997, the season after the Packers won Super Bowl XXXI.

The quality of Reid's work with the Packers attracted considerable notice throughout the league, leading to his hiring as the head coach of the Philadelphia Eagles on January 11, 1999. Beginning in 2001, Reid's Eagles won the National Football Conference's Eastern Division four consecutive times, the longest such streak in franchise history, and advanced to the conference championship game in 2001, 2002, 2003 and 2004, losing this game on the first three occasions. The Eagles made it to Super Bowl XXXIX but fell to the New England Patriots 24-21 in the final minutes.

In the 2008 season, Reid led the Eagles to a 5th NFC Championship game, where they lost to the Arizona Cardinals 32-25. He also coached the NFC to a 30-24 win in the 2009 Pro Bowl. Reid was again named the Earle "Greasy" Neale Award winner for the third time in 2010.

In 2001, Reid was named executive vice president of football operations of the Eagles, effectively making him the team's general manager. In 2013, after many years in Philadelphia, he was named Head Coach of the Arizona Cardinals.