While playing college football at Clemson, Whitehurst became the first quarterback to go 4–0 in the rivalry between Clemson and the University of South Carolina, including a 63–17 rout of the Gamecocks in Columbia on November 22, 2003. The following year, he was used as a multiple weapon by Tommy Bowden and the Tigers offense. In addition to passing for 2,067 yards, seven touchdowns, and 17 interceptions, he had one punt for 25 yards and also had a two-yard reception. Whitehurst graduated from Clemson in December 2004 with a bachelor's degree in marketing and began graduate school by the start of his senior season in 2005. Whitehurst left Clemson with 9,665 passing yards, 49 touchdowns and 46 interceptions and a 124.2 quarterback rating. On the ground, he gained 98 yards on 266 attempts and 10 touchdowns.
College statistics
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Professional career
San Diego Chargers
Whitehurst was drafted by the San Diego Chargers in the third round of the 2006 NFL Draft. He played in two regular season games as the third-stringer to Billy Volek and starter Philip Rivers. His first career appearance was in Week 2 against the Tennessee Titans in 2006. Whitehurst rushed once for 14 yards and a touchdown in a 40–7 win. His second appearance came in Week 5 at San Francisco, which also resulted in a win, 48–19. He had one rush for a one-yard loss. He entered two more games but did not record a stat, Week 8 against the Cleveland Browns and Week 12 in a 24–21 win against the Buffalo Bills. From 2007 to 2009, he did not enter another NFL game.
Seattle Seahawks
Whitehurst was traded to the Seattle Seahawks on March 17, 2010, in exchange for a 2011 third-round draft pick to San Diego, and the two teams switched second-round picks in the 2010 NFL Draft. He was signed to a two-year, $8 million contract. Seattle's front office later stated they had already picked up a potential franchise quarterback in the draft by acquiring Whitehurst with the 2011 selection. On November 7, 2010, Whitehurst made his first-career start and completed 12-of-23 passes for 113 yards with a touchdown and two interceptions in a Week 9 loss against the New York Giants due to an injury suffered by starting quarterback Matt Hasselbeck. Whitehurst started on January 2, 2011, in a Sunday Night Football game against the division rival St. Louis Rams to determine the NFC West champion. Whitehurst was five-for-five for 85 yards on the opening drive and finished the first half going 16-for-21 with 138 yards and one touchdown. He finished the game 22-of-36 and 192 yards. Hasselbeck returned as the starter for the subsequent playoff game. Prior to the 2011 preseason, Whitehurst was named the backup to Tarvaris Jackson, the former Vikings quarterback whom Seattle acquired in the 2011 offseason. However, Jackson and Whitehurst were expected to compete for the starting job once Whitehurst became familiar with the new offensive schemes. Whitehurst went 14-of-19 passing with one touchdown to put Seattle on the board against the Vikings in 2011's second preseason action. Whitehurst took over for an injured Jackson during a Week 5 matchup at the New York Giants. In that game, Whitehurst outscored Jackson's 14 points in the first three quarters by putting up 20 points in the fourth quarter, going 11-for-19, 149 yards, and a 27-yard touchdown pass to Doug Baldwin, securing a 36–25 Seattle victory. Coach Pete Carroll named Whitehurst the starting quarterback until Jackson healed from a pectoral injury, although no official date of Jackson's medical clearance had been released. Whitehurst was named the starter for Week 7 against the Cleveland Browns, because Jackson had suffered a pectoral injury against the Giants. Whitehurst went 12-of-30 for 92 yards, with no touchdowns and two turnovers. Whitehurst started in Week 9 against the Cincinnati Bengals, but was benched for an injured Jackson after going 4-of-7 for 52 yards.
San Diego Chargers (second stint)
On March 16, 2012, Whitehurst signed a two-year contract to reunite with his former team, the San Diego Chargers.
Tennessee Titans
On March 13, 2014, Whitehurst signed a two-year contract with the Tennessee Titans replacing Ryan Fitzpatrick as the backup quarterback. Whitehurst appeared in seven games with five starts and recorded career-highs in completions, pass attempts, passing yards, touchdowns, and an 87.4 passer rating while rushing 20 times for 90 yards. He recorded a career-high two touchdown passes against the Cleveland Browns on October 5, 2014. He posted a career-best 287 passing yards against the Jacksonville Jaguars on December 18, 2014. Whitehurst made the start in Week 4 against the Indianapolis Colts after Jake Locker's injury, his first start since Week 8 of the 2011 season. He was waived by the team on November 11, 2015.
Indianapolis Colts
On November 12, 2015, Whitehurst was claimed off waivers by the Indianapolis Colts. Whitehurst's best game of the season was on December 27, 2015, against the Miami Dolphins, completing 9-of-14 passes for 78 yards and a 78.9 passer rating. He appeared in four games for the Colts before being placed on injured reserve on December 28, 2015.
Cleveland Browns
Whitehurst signed with the Cleveland Browns on September 19, 2016. After starting quarterback Cody Kessler was injured in the first quarter of the Week 5 game against the New England Patriots, Whitehurst completed 14-of-24 passes for 182 yards with a touchdown and an interception as the Browns lost by a score of 33–13. Whitehurst also hyperextended his left knee late in the fourth quarter but returned for the final play of the game, which was a kneel down. On October 11, 2016, he was released by the Browns with an injury settlement.