Pace played college football for the Ohio State Buckeyes, where he twice received unanimous All-American honors, and was selected by the Rams first overall in the 1997 NFL draft.

He spent all but one season of his professional career in St. Louis, concluding his NFL tenure as a member of the Chicago Bears.

Pace was so dominant that the term pancake block—referring to when an offensive lineman knocks a defender on his back—gained popularity at Ohio State due to his play.

In fact, the Ohio State Athletic Department distributed Orlando Pace pancake magnets as a promotion for his Heisman Trophy run.

Pace finished fourth in the Heisman trophy race in 1996,[5] which was practically unheard of for an offensive lineman, and demonstrated his dominance at the college level.

In 1999, Pace was selected as a starting offensive tackle by Sports Illustrated in their "NCAA Football All-Century Team".

Pace was one of five Ohio State Buckeyes on Sport Illustrated's All-Century Team 85-man roster; the others being Jim Parker, Archie Griffin, Chris Spielman, and Jack Tatum.

[1] Pace was one of three Rams' offensive linemen (C Andy McCollum, RT Ryan Tucker) who were not penalized for holding.

He started all three playoff contests, the St. Louis Rams claimed the NFC West title and advanced to Super Bowl XXXVI falling to the New England Patriots, 20–17.

[1] Pace had a lengthy holdout by reporting to camp on August 26, 2003, and signing a one-year deal as the Rams franchise player.

He earned a fifth consecutive Pro Bowl invitation as the Rams claimed their third NFC West title in five years.

By designating Pace as a franchise player, the Rams were obligated to pay him the average salary of the five highest-paid offensive linemen in the NFL.

He was one of three linemen to start every game (C Andy McCollum, G Adam Timmerman) and blocked for an offense that ranked eighth in the NFL (third in the NFC) in first downs (321).

[1] Pace helped Rams convert 13-of-16 fourth down attempts, second highest fourth-down conversion percentage in the NFL (68.4%).

[1] In 2006, Pace started the 8 games he appeared in until he left in the second quarter against the Seattle Seahawks on November 12, 2006, after he tore his triceps, ending his 2006 season.

Dogged by injuries in recent seasons, Pace was released by the Rams on March 10, 2009,[13] to save $6 million under the salary cap.

Pace started the first 11 games at left tackle in his lone season with the Bears in 2009 before sustaining a groin injury on November 29 in a loss to the Minnesota Vikings.