He spent most of his 13-season career as a backup to Brett Favre on the Green Bay Packers, where he was a member of the team that won Super Bowl XXXI.

Pederson was also a backup to Dan Marino on the Miami Dolphins and a starter for the Philadelphia Eagles and Cleveland Browns until retiring in 2004.

[7] After spending the 1991 season as a free agent, the New York/New Jersey Knights of the World League of American Football (WLAF) drafted him in the fifth round for the first pool of draft-eligible players on February 4, 1992.

[14] Dan Marino, the Dolphins' starting quarterback since 1983, ruptured his Achilles' tendon in a week 6 game against the Cleveland Browns on October 10, 1993, forcing backup Scott Mitchell to replace him.

[19] Mitchell returned as the Dolphins' starter after week 15, and Pederson was released in favor of backup DeBerg and third-string quarterback Hugh Millen on December 16, 1993.

[21] He spent the entire 1994 season on the Dolphins' active roster as the third-string quarterback behind Marino and Bernie Kosar.

On February 15, 1995, Pederson was selected by the Carolina Panthers in the twenty-second round of the NFL Expansion Draft,[22] after being placed on the Dolphins' available players list on January 19,[23] but was released on May 24, 1995.

Third-string quarterback T. J. Rubley was forced to play in week 10 and threw a game-ending interception after calling an audible, going against head coach Mike Holmgren's playcall.

[31] The Packers claimed Jim McMahon off waivers from the Browns to serve as Favre's backup ahead of Pederson and Rubley on November 29, 1995.

In a week 5 loss to the Minnesota Vikings, Pederson replaced Favre in the last five minutes of a blowout game, and threw two touchdowns in his place.

In his first career start, a week 1 game against the Arizona Cardinals, Pederson threw two touchdowns in the first quarter to help give the Eagles a 21–0 lead.

[41] Pederson started a week 3 shutout loss (26–0) to the Buffalo Bills, going 14-of-26 for 137 yards and two lost fumbles, before being replaced by McNabb again in the fourth quarter.

In his final start as an Eagle, Pederson was benched at halftime of a week 9 game against the Carolina Panthers after going 3-of-9 for 28 yards and being down 23–0.

Pederson went 8-for-12 for 108 yards and a touchdown in the loss, and Koy Detmer received the start ahead of him in week 15 with McNabb still injured.

[45] Pederson considered retirement after being released by the Eagles, but instead signed a two-year contract with the Cleveland Browns on September 2, 2000.

[29] The Packers re-signed Pederson to a one-year contract on March 13, 2001, to replace backup Matt Hasselbeck, who was traded to the Seattle Seahawks.

[53] Tim Couch was signed to compete for the backup quarterback job, but lost out to Pederson and was released on September 5, 2004.

[59] After his retirement, Pederson was hired as head coach of Calvary Baptist Academy, a private Christian high school in Shreveport, Louisiana.

[65] Despite having Sam Bradford on the roster as the starting quarterback, the Eagles drafted Carson Wentz with the second overall pick in 2016.

[66] Right before the 2016 season began, Bradford was traded to the Minnesota Vikings and Wentz was named the starting quarterback as a rookie.

[68][69] Pederson's second season was much more successful as he led the Eagles to a 13–3 record, winning them the NFC East division championship and allotting them home-field advantage throughout the playoffs.

[74] Foles, the eventual Super Bowl MVP, led the team to a 41–33 win over the New England Patriots, giving them their first Lombardi Trophy in franchise history and their first league championship since 1960.

After winning their last game against the Washington Redskins and the Minnesota Vikings losing to the Chicago Bears, the Eagles made it back to the playoffs with a 9–7 record as the sixth seed.

[81] During the final ten seconds of the game, Pederson called a timeout before Bears placekicker Cody Parkey could score the game-winning field goal, negating his successful attempt.

Although Pederson said the decision was to give Sudfeld the opportunity to play, he was accused of deliberately losing the game to increase the Eagles' draft position.

[99] The Jaguars became the third team since the 1970 AFL–NFL merger, along with the 2004 San Diego Chargers and the 2008 Miami Dolphins, to draft first overall and then win their division in the following season.

Following a loss to the Tennessee Titans in Week 18, the Jaguars fell to a final record of 9–8 and missed the playoffs and the chance to win the AFC South, finishing second behind the Houston Texans.

An embarrassing 52–6 loss to the Detroit Lions in Week 11 fueled reporters' speculation that "the end could be nigh" for Pederson's job.

[105] He continued to coach the Jaguars but was fired the morning after the team's final game of the 4–13 season that, as reported, "fell seismically short of owner Shad Khan's expectations.

A devout Christian,[107] Pederson and his wife Jeannie have three sons, including Josh, also a professional football player.