Anderson attended Jesse M. Bethel High School in Vallejo, California, where he rushed for nearly 4,000 yards during his high school career as he led his squad to four consecutive playoff appearances, including a spot in the Sac-Joaquin Section title game as a junior in 2007, when he was named the Vallejo Times-Herald Athlete of the Year. He was a two-time Vallejo Times Herald MVP and first-team selection, while also picking up first-team All-Solano County Athletic Conference honors in both his junior and senior campaigns. He posted 1,297 rushing yards and 20 touchdowns on the ground and completed 44-of-91 passes for 785 yards and 11 scores as a junior. As a senior, he moved to running back after playing quarterback in an option offensive during his junior campaign and rushed for 1,623 yards and 23 touchdowns on the ground, while also contributing with 2 interceptions on defense. He became the first Bethel player to sign with and play for a Pac-12 school. Anderson also participated in track, posting bests of 12.11 seconds in the 100-meter dash and 24.35 seconds in the 200-meter dash.
Anderson was selected to the first-team All-American, All-State, and All-NorCal Conference teams while at Laney College in Oakland, California. He went on to play at California. In his first year at Cal as a junior in 2011, Anderson had 72 carries for 345 yards and 8 touchdowns on the ground and 7 receptions for 186 yards and one touchdown through the air. As a senior, he produced 126 carries for 790 yards and 4 touchdowns plus 15 catches for 164 yards and a touchdown.
Anderson signed with the Denver Broncos as an undrafted free agent on March 17, 2013. Anderson was injured during Denver's preseason. Anderson made his NFL debut on October 27, 2013, running for 22 yards on 4 carries against the Washington Redskins. The Broncos reached Super Bowl XLVIII in Anderson's rookie season but lost 43–8 to the Seattle Seahawks. Anderson had a reception for 14 yards and two carries for nine yards as he got the ball for the last three times of the game.
On November 9, 2014, Anderson scored his first career touchdown, on a 51-yard screen pass from Peyton Manning in a 41–17 rout of the Oakland Raiders. Anderson also ran for 90 yards on 13 carries. On November 23, 2014, Anderson ran for 167 yards on 27 carries and a touchdown against the Miami Dolphins. Anderson's performance was his first game of his career with over 100 rushing yards. On November 30, 2014, Anderson ran for a season-high 168 yards and a receiving touchdown against the Kansas City Chiefs. Anderson caught a 15-yard touchdown reception. Anderson ran for over 150 yards each time, the first Denver Broncos running back to do so since 2004. On December 7, 2014, Anderson scored 3 touchdowns against the Buffalo Bills. This was Anderson's first multi-touchdown game of his career. On December 22, 2014, Anderson ran for 83 yards and a touchdown against the Cincinnati Bengals. Anderson ran for his 5th touchdown of the season. On December 28, 2014, Anderson ran for another 3 touchdowns against the Oakland Raiders, bringing his total touchdown total to 10. On January 11, 2015, Anderson ran for 80 yards on 18 carries against the Indianapolis Colts in the first round of the playoffs. The Broncos lost 13-24. Anderson was ultimately named to his first Pro Bowl at the end of the season in place of the injured Le'Veon Bell.
On November 1, 2015, Anderson ran for 101 yards on 14 carries and a touchdown against the Green Bay Packers. Anderson scored on a 28-yard run. On December 2, 2015, after a 30–24 win against the New England Patriots in Week 12, Anderson was named the AFC Offensive Player of the Week. Anderson compiled 113 rushing yards and 2 touchdowns, including the game-winning score. The Broncos finished the season 12–4 and Anderson had 720 rushing yards with 5 touchdowns. The Broncos earned the No. 1 seed in the AFC. On January 17, 2016, Anderson had 15 carries for 72 yards and the game-winning touchdown in the first playoff game, against the Pittsburgh Steelers. The Broncos won 23–16. In the AFC Championship game against the New England Patriots, Anderson had 16 carries for 72 yards. The Broncos won 20–18 to advance to the Super Bowl. On February 7, 2016, Anderson was a key contributor in the Broncos' 24-10 victory over the Carolina Panthers in Super Bowl 50. In the game, Anderson totaled 100 yards of offense on 27 touches (23 carries and four receptions), one of his carries being a two-yard touchdown run with less than three minutes left, expanding the Broncos' lead to twelve points.
After the 2015 season, Anderson became a restricted free agent and signed a four-year, $18 million offer sheet with the Miami Dolphins on March 10, 2016. However, on March 15, 2016, the Broncos matched the Dolphins' offer, keeping Anderson in Denver for the next four seasons.
On September 8, 2016, Anderson ran for 92 yards on 20 carries and two touchdowns (1 rushing, 1 receiving) in the season opening Super Bowl 50 rematch against the Carolina Panthers. Anderson had a 25-yard touchdown reception and a 28-yard run. On September 18, 2016, Anderson ran for 74 yards and a touchdown against the Indianapolis Colts. On October 2, 2016, Anderson ran for his third touchdown of the season against the Tampa Bay Buccaneers. On October 24, 2016, Anderson injured his knee early in the Week 7 game against the Houston Texans but continued to play in the game. Anderson ran for 107 yards on 16 carries and a touchdown. He reported soreness to the team doctors on Tuesday and underwent surgery to repair his meniscus that week. He had 110 carries for 437 yards and four touchdowns along with 16 receptions for 128 yards and a touchdown. He was placed on injured reserve on October 29, 2016 and underwent successful surgery.
Anderson is a long-time fan of the video game series, Sonic the Hedgehog. He shows his fandom by wearing shirts of it under his uniform jersey, as well as speaking about it occasionally on his Twitter account. Anderson was also once given a box of merchandise from Sega such as a backpack.