After he was chosen in the third round (73rd overall) of the 2002 NFL Draft out of Georgia, Will Witherspoon stepped straight into the middle of Carolina's defense during John Fox’s first season as head coach. Taking over the starting middle linebacker role as a rookie, Witherspoon provided an athletic, high-IQ presence that transformed Carolina's linebacking corps.

Witherspoon brought secondary-like lateral agility and explosive closing speed to the second level. Operating as the middle linebacker before shifting to weakside linebacker, his defining strength was his range—sliding through traffic to blow up perimeter runs and dropping into intermediate passing lanes to swallow up tight ends and running backs in coverage.

Witherspoon blossomed in his second season (2003), serving as a cornerstone of a Carolina defense that ranked second overall in the NFL. Starting all 16 games, he racked up 100 total tackles (73 solo), 1.5 sacks, and two interceptions. His dynamic play alongside Dan Morgan and Mark Fields helped power the Panthers through the playoffs, culminating in the franchise's first Super Bowl appearance, Super Bowl XXXVIII.

Witherspoon elevated his production even higher over his next two seasons in Charlotte. In 2004, he led the team with a career-high 104 total tackles while adding 3.0 sacks, four forced fumbles, and two interceptions. He backed that up in 2005 with 81 tackles, 2.5 sacks, and two interceptions across 15 starts, helping guide Carolina back to the NFC Championship Game.

After the 2005 postseason, Witherspoon became a free agent and signed a multi-year deal with the Rams, later playing for the Eagles and Titans before ending his 12-year NFL career. In four seasons with the Panthers (2002–2005), he played in 60 regular-season games (55 starts) and seven playoff games, recording 354 tackles (259 solo), 8.0 sacks, six interceptions, 28 passes defensed, six forced fumbles, and three recoveries.