In 2000, Pierce played college football at the University of Arizona, playing in eleven games and made 77 total tackles, three sacks, two forced fumbles and an interception. Previously to attending the University of Arizona, he had attended and played football for Mount San Antonio College in Walnut, California.
Pierce entered the NFL in 2001 as an undrafted free agent and was signed by the Washington Redskins on April 22, 2001. A surprise starter on a Redskins defense in his rookie season, Pierce played in all sixteen of the Redskins games in 2001 (seven starts) and made 52 total tackles, one sack and an interception. For the next two seasons, 2002 and 2003, he played in 23 games, mostly on special teams however. In 2004, Pierce, for the first time since his rookie season became a major player in the Redskins defense. Playing and starting all sixteen of the Redskins 2004 regular season games as the teams middle linebacker, Pierce made 112 total tackles, one sack and two interceptions; one of which he returned 78 yards for a touchdown.
After his contract with the Redskins expired after the 2004 season, Pierce signed with the New York Giants on March 3, 2005. In his first season with the Giants he started all thirteen of the games he played with the Giants before suffering a season ending ankle injury in a regular season week 14 vs the Philadelphia Eagles. Despite the fact that he missed the last three games of the season he still led the Giants in tackles with 99 and made the NFC Pro Bowl team. In 2006, he rebounded from his injury and played and started all sixteen of the Giants regular season games and one postseason game (which the Giants lost to the Philadelphia Eagles). He made 137 total tackles (one of the best totals for an NFC defensive player), one sack, an interception and for the second straight year was named to the NFC Pro Bowl team.