He played college football for the Oregon State Beavers and was selected in the first round of the 2004 NFL draft by the Rams, where he spent his first nine seasons.

Named to three Pro Bowls and two All-Pro teams during his Rams tenure, Jackson is the franchise's all-time leading rusher.

Jackson was born in Las Vegas, Nevada, and was a running back for Eldorado High School.

Eldorado lost in the state final his senior year to McQueen High School (Reno, Nevada).

He also lettered four years in track and field, recording a 10.6 in the 100 meters as a junior, and was a member of the 4 × 100 m (42.64 s) relay squad.

[1] Jackson's subsequent success has been credited with prompting college football programs to take more interest in players in the Las Vegas area.

[6] When his collegiate career ended, Jackson's 2,015 all-purpose yards set an Oregon State school record.

[7] Jackson was overlooked by several teams in 2004, most likely due to a knee injury suffered during his last year at Oregon State that kept him from participating in drills at the 2004 NFL Combine.

In an interview with CBS Sports' Pete Prisco on how the knee injury had affected his play, Jackson said, "I never felt right.

[13] He made his NFL debut in the season opener against the Arizona Cardinals and had seven carries for 50 yards in the 17–10 victory.

[23] After the dismissal of head coach Mike Martz and the departure of Faulk, 2006 became Jackson's breakout season.

For his efforts, Jackson was named to his first Pro Bowl and received one vote for the 2006 NFL Offensive Player of the Year award.

[40] During the Rams' dismal 2007 season, Jackson lashed out at fans and expressed distaste with the music played in the Edward Jones Dome.

[42] After the season, with one year left on his rookie contract, Jackson believed he was underpaid and held out of training camp.

[43] Because the final two years of the deal (2012 and 2013) can be voided based on Jackson's performance, it could become a three-year extension worth $29.3 million instead.

[58] He rushed for over 100 in three consecutive games against the Detroit Lions, San Diego Chargers, and the Tampa Bay Buccaneers.

[59][60] Jackson surpassed Eric Dickerson as the Rams' all-time leading rusher, with a 110-yard effort against the Buccaneers game.

[71] With the retirement of LaDainian Tomlinson, Jackson became the NFL's active leader in career rushing yards, where he remained for over three years until passed by Frank Gore in October 2015.

[74] At the conclusion of the season, Jackson chose to opt-out of the final year of his contract, to pursue a starting job on a contender.

[83] On July 29, 2019, Jackson signed a ceremonial one-day contract with the by-then Los Angeles Rams to officially retire as a member of the team.