Woodhead played football at North Platte High School in North Platte, Nebraska, and broke many records. North Platte reached the state finals in 2001, with Woodhead’s help after beating Millard North High School team 24–21. Woodhead blocked a field goal attempt late in the fourth quarter to give North Platte possession with only minutes left. North Platte’s Ben Woodhead, Woodhead’s older brother, threw a pass down field to set up a game-winning field goal by Jake McCarthy. However, North Platte went on to lose the state championship 28–14 to Millard West High School.

Through 39 games, Woodhead’s 606 points equated to 15.5 points a game, the highest ever in NCAA Division II. Only Dan Pugh of Mount Union College, a Division III school in Ohio, with 248 points in 2002 and Barry Sanders of Oklahoma State with 234 in 1988, had ever scored more points in a season than Woodhead scored in 2006. However, in 2007 Abilene Christian University’s Bernard Scott broke Woodhead’s Division II record by scoring 39 touchdowns (234 points).

In 2004, Woodhead began attending Chadron State College in Chadron, Nebraska, where he rushed for 1,840 yards as a true freshman. Woodhead was the first recipient of a full athletic scholarship at Chadron State in its 96-year history.

Woodhead was a Harlon Hill Trophy candidate in 2004, 2005, 2006, and 2007, winning the award in both 2006 and 2007.

In 2005, Woodhead carried the ball 278 times for 1,769 yards, averaging 6.4 yards per carry, and 21 touchdowns. He also had 30 receptions for 367 yards, averaging 12.2 yards per reception.

In 2006, through 12 games, Woodhead rushed for 2,740 yards, a new all-division single season rushing record, surpassing Kavin Gaillaird. Including the playoffs, his rushing yards in 2006 totaled 2,756. He also led his team to the NCAA Division II playoffs in 2006, losing to Northwest Missouri State. Northwest Missouri State managed to hold Woodhead to a season low 16 yards rushing on 16 carries while giving up 79 yards receiving, which was more than double anyone on the Northwest Missouri team. Chadron also had 327 yards of total offense compared to Northwest Missouri State’s 306.

Barry Sanders is the only college player to accumulate more all-purpose yards than the 3,159 that Woodhead gained in 2006, as he gained 3,250 as a junior at Oklahoma State University in 1988, when he won the Heisman Trophy. Woodhead ranked 10th in Division-II in career all-purpose yards with 7,349 after his junior season. The Division-II leader is Brian Shay of Emporia State with 9,301 yards, including 1,207 on kickoff returns, 1995–1998.

After a 208-yard game against Western New Mexico in 2007, he became college football’s all-time leading rusher, breaking the record previously held by R.J. Bowers, who played for Grove City College, a Division III school in Pennsylvania from 1997–2000. Woodhead is also just the sixth NCAA Division II player to rush for more than 1,000 yards in four seasons.

Woodhead did not receive an invite to the NFL Scouting Combine, so he had to use his pro day to show his abilities. According to a report on NFLDraftWatch.net, he ran the 40-yard dash in times of 4.33 to 4.38 seconds, which would have been the second-fastest among all running backs at the NFL Combine in March 2008. He posted the best pro-agility time of 4.03 seconds, the second-best vertical jump (38½ inches) and the best 60-yard shuttle time (11.2 seconds). He also bench pressed 225 pounds 20 times.

Woodhead went undrafted in the 2008 NFL Draft. However, he received a call from the New York Jets moments before the draft ended, about the two parties coming to an agreement on an undrafted rookie free agent contract. It was announced shortly after, that Woodhead had signed a deal with the organization.

On July 26, 2008, Woodhead was waived/injured by the Jets after being carted off the field due to an injury. He spent his entire rookie season on injured reserve.

On September 3, 2009, the Jets faced the Philadelphia Eagles in a preseason matchup. During this game, Woodhead rushed for 158 yards, the NFL’s second-highest preseason total since 1992, and two touchdowns. Woodhead initially survived final cuts in September 2009, only to be waived a day later on September 6. He was re-signed to the Jets’ practice squad on September 8. In October, Woodhead was moved from running back to wide receiver and on October 17, he was signed to the active roster after Jerricho Cotchery and Brad Smith became injured.

Woodhead saw his first regular season action on October 25, 2009. In the 38–0 win over the Oakland Raiders, Woodhead rushed three times for 24 yards. Overall, he finished the 2009 season with 15 carries for 64 rushing yards and eight receptions for 87 receiving yards.

Woodhead was released by the Jets on September 14, 2010.

Woodhead was signed by the New England Patriots on September 18, 2010, one day before the team’s Week 2 matchup against the Jets. The team had an open roster spot for Woodhead after the trade of Laurence Maroney; Woodhead was inactive for the game, which saw longtime Patriots third-down running back Kevin Faulk go down for the season with a knee injury. On September 26, making his Patriots debut as well as his first career start, Woodhead had a 22-yard touchdown run against the Buffalo Bills, his first NFL touchdown. In Week 4, Woodhead added an 11-yard touchdown reception in a win over the Miami Dolphins. Against the Indianapolis Colts in Week 11, Woodhead had a 36-yard touchdown run in a Patriots win.

On November 19, 2010, Woodhead signed a two-year contract extension with the Patriots, through the 2012 season.

In the 2011 season, Woodhead had 77 carries for 351 rushing yards and a touchdown to go along with 18 receptions for 157 yards. The Patriots finished with a 13–3 record and won the AFC East. In the Divisional Round against the Denver Broncos, he had four carries for 25 yards in the 45–10 victory. In the AFC Championship, he had six carries for 18 yards and a seven-yard reception in the 23–20 victory over the Baltimore Ravens. On February 5, 2012, he made a catch in the second quarter of Super Bowl XLVI to score the first touchdown in the game for the Patriots. New England would eventually lose the game to the New York Giants 21–17. Woodhead finished with four catches for 42 yards and a touchdown while rushing seven times for 18 yards.

In the 2012 season, Woodhead had 76 carries for 301 yards and four touchdowns to go along with 40 receptions for 446 yards and three touchdowns.

Woodhead agreed to terms with the San Diego Chargers on March 15, 2013. He signed a two-year, $3.5 million contract. The deal included a $1 million signing bonus. He scored his first touchdown as a Charger in a Week 4 matchup against the Cowboys. The Chargers won the game and Woodhead ended up with two touchdown catches. Sharing time with Ronnie Brown as the team’s backup to Ryan Mathews, Woodhead enjoyed a career year. He led all NFL running backs with six touchdown receptions and was second with 76 catches for 605 yards in the regular season. He also had 106 carries for 429 yards, averaging 4.0 yards per attempt, for an overall 1,034 yards and eight touchdowns; he added a dimension missing in San Diego’s offense since Darren Sproles departed after 2010. Of all the Chargers free agent acquisitions in 2013, quarterback Philip Rivers said he “was most excited about” Woodhead.

Against the Buffalo Bills in Week 3 of 2014, Woodhead suffered a leg and ankle injury and was carted off the field. His season ended after he was diagnosed with a broken fibula. In limited time in the 2014 season, he had 38 rushing yards and five receptions for 34 yards.

After recovering from a broken fibula, Woodhead had a strong showing against the Detroit Lions, rushing for 43 yards and scoring two touchdowns. Against the Cleveland Browns, Woodhead had 54 rushing yards that included a 19-yard rush that set up a game-winning field goal by Josh Lambo and also had 84 receiving yards, one of those catches being for 61 yards, the longest of his career. Against the Miami Dolphins, Woodhead scored three touchdowns on six receptions, and another touchdown running the ball for a single-game career-high for touchdowns in a game. He scored 24 total points in the game, which was the most by any player in a single game in the 2015 season. Overall, he finished the 2015 season with 98 carries for 336 rushing yards and three touchdowns to go along with 80 receptions for 755 receiving yards and six touchdowns.

In the 2016 Week 2 matchup against the Jacksonville Jaguars, Woodhead suffered a torn ACL and was placed on injured reserve, ending his season.

On March 9, 2017, Woodhead signed a three-year contract with the Baltimore Ravens. In Week 1, Woodhead suffered a hamstring injury on the Ravens’ opening drive and was initially ruled out for 4–6 weeks. On September 14, 2017, Woodhead was placed on injured reserve, causing him to miss at least eight weeks. He was activated off injured reserve to the active roster on November 18, 2017.

On March 13, 2018, Woodhead was released by the Ravens. Later that week, on March 17, Woodhead announced his retirement after 10 seasons in the league.