He was born Todd Jerome Gurley II in Baltimore. He attended Tarboro High School in Tarboro, North Carolina, where he was a three-sport star in football, basketball, and track. He played running back and defensive back for the Vikings during his junior season, totalling 1,472 rushing yards and 26 touchdowns, as well as 79 tackles, an interception, and a forced fumble. He was named Rocky Mount Telegram All-Area Offensive Player of the Year for the 2010 season. As a senior in 2011, he was the North Carolina Associated Press Player of the Year after totaling 2,600 yards and 38 touchdowns. Gurley helped the Vikings football team win the 2A North Carolina state championship, rushing for 242 yards and four touchdowns in the championship game against Lincolnton High School. During his sophomore year, he was Special Teams player on the 2009 State Championship team. During his junior year he led the Vikings to a state championship.

In the 2012 season, Gurley started 12 of 14 games and rushed for 1,385 yards on 222 carries with 17 rushing touchdowns. After the season, Gurley was named First-Team All-SEC by the Associated Press. He was one of two true freshman running backs to accomplish this feat in 2012, the other player being T. J. Yeldon of Alabama.

On August 31, in Georgia’s season opener at Clemson’s Memorial Stadium, Gurley led the Bulldogs with a career-high 154 rushing yards on 12 carries and two rushing touchdowns. Even though the Bulldogs lost the game 38–35, Gurley had an impressive performance against Clemson which included a 75-yard touchdown run early in the first quarter. In the following game against rival South Carolina, he had 30 carries for 132 rushing yards and one rushing touchdown to go along with an eight-yard receiving touchdown in the 41–30 victory. On November 2, against Florida, he had 17 carries for 100 rushing yards and a rushing touchdown to go along with three receptions for 87 receiving yards and one receiving touchdown in the 23–20 victory. On November 30, against Georgia Tech, he had 20 carries for 122 rushing yards and three rushing touchdowns to go along with four receptions for 36 receiving yards and one receiving touchdown in the 41–34 victory. In the 2014 Gator Bowl against Nebraska, he had 86 rushing yards and 97 receiving yards and a receiving touchdown in the 24–19 loss. In ten games, he rushed for 989 rushing yards on 165 carries with ten rushing touchdowns to go along with 37 receptions for 441 receiving yards and six receiving touchdowns. After the season, Gurley was named Second-Team All-SEC by the Associated Press.

Gurley was selected in the first round with the 10th overall pick by the St. Louis Rams in the 2015 NFL Draft. He was the first running back to be selected in that year’s draft. Gurley’s rehabilitation went ahead of schedule and during the team’s preseason, while he did not play, he practiced without wearing pads. Shortly after, Gurley was medically cleared for full contact by St. Louis team physicians.

On September 27, 2015, Gurley made his NFL debut against the Pittsburgh Steelers. He was eased into action and finished the game with six rushes for nine yards in the 12–6 loss. The following week, the Rams visited the undefeated Arizona Cardinals for an NFC West divisional matchup. Gurley started slow with just two rushing yards at halftime, but rushed for 144 yards in the second half as the Rams edged the Cardinals by a score of 24–22. The next three games against the Green Bay Packers, Cleveland Browns, and the San Francisco 49ers would see Gurley rush for at least 128 rushing yards per game. He scored his first NFL touchdown on October 25, 2015 against the Browns. With 566 yards in his first four NFL starts, Gurley became the most prolific rusher in his first four NFL games since the AFL–NFL merger. Following the 27–6 win over the 49ers in Week 8, Gurley’s jersey and cleats were inducted into the Pro Football Hall of Fame.

Gurley finished his rookie year with 1,106 rushing yards and ten touchdowns on 229 attempts despite making only 12 starts (he sat out the Rams’ season-ending loss at San Francisco). On December 22, 2015, Gurley was selected to be part of the 2016 Pro Bowl along with fellow Rams players defensive lineman Aaron Donald and punter Johnny Hekker. Gurley was one of the five rookies to be selected to the Pro Bowl, along with Kansas City Chiefs cornerback Marcus Peters, Seattle Seahawks wide receiver/kick returner Tyler Lockett, Oakland Raiders wide receiver Amari Cooper, and Tampa Bay Buccaneers quarterback Jameis Winston. Gurley beat out Winston for NFL Offensive Rookie of the Year, earning a decisive 27 votes to 17 for Winston. He was ranked 22nd by his fellow players on the NFL Top 100 Players of 2016.

Following the Rams’ Week 8 bye, Gurley’s output became more balanced for the next five games: he averaged 62 rushing- and 54 receiving-yards per game, with 100+ yards from scrimmage in four of them, and recording three touchdowns (all rushing) over that time period. In Week 14, he had 96 rushing yards and two touchdowns on just 13 carries, along with 39 receiving yards in an impressive-but-losing effort against Philadelphia. In Week 15, Gurley had a career-best four touchdowns (three rushing, including a 57-yarder on 3rd and 20 with 30 seconds left in the first half) on 180 yards from scrimmage in a dominant 42–7 win over Seattle. He scored 24 total points in the game, which was the most for a single game by any player in the 2017 season. His performance in Week 15 earned him NFC Offensive Player of the Week. On December 19, 2017, Gurley was named to his second Pro Bowl as a starter. In Week 16, Gurley caught 10 passes for 158 yards and two touchdowns to go along with 122 rushing yards (1st and 3rd in the NFL that week respectively), earning him NFC Offensive Player of the Week for the second straight week. Gurley was also named the NFC Offensive Player of the Month for the second time that season. The playoff-bound Rams decided to have Gurley sit out the last game of the season against the San Francisco 49ers, allowing Kareem Hunt to win the title for rushing yards, but he still led the NFL with 13 rushing touchdowns, 19 total touchdowns, and 2,093 yards-from-scrimmage and all-purpose yards. He finished the season leading the league in scoring among non-kickers with 114 points. He was the 16th player in NFL history with a 750/750 rushing/receiving yard season (8th at 1,300/750).

Gurley played his first career post-season game in the Wild Card Round against the Atlanta Falcons on January 6, 2018. Playing from behind most of the game, he had 14 carries for 101 yards in the 26–13 loss.

On April 24, 2018, the Rams exercised the fifth-year option on Gurley’s contract. On July 24, 2018, Gurley signed a four-year, $60 million contract extension with the Rams with $45 million guaranteed, making him the highest-paid running back in the NFL.

With a 17-yard touchdown run during a Week 10 victory over the Seattle Seahawks, Todd Gurley set a new team record by scoring a touchdown in 13 straight games, breaking the mark set by Elroy “Crazy Legs” Hirsch. During a Week 12 matchup against the Detroit Lions, Gurley rushed for 132 yards and two touchdowns in the fourth quarter to help the Rams clinch their second straight NFC West title and was named NFC Offensive Player of the Week for the second time in 2018.

In the NFC Championship Game against the New Orleans Saints, Gurley struggled as he ran four times for 10 yards and a touchdown and had one catch for three yards in a 26–23 overtime victory to advance and play the New England Patriots in Super Bowl LIII. Leading up to the Super Bowl, Gurley’s injury status was heavily discussed with reports claiming he was healthy while other reports claimed his knee was significantly more hurt than thought. In the Super Bowl, Gurley had ten carries for 35 rushing yards in the 13–3 loss to the Patriots. On March 2, 2019, it was reported that Gurley has arthritis in his left knee.

In Week 2 against the New Orleans Saints, Gurley rushed 16 times for 63 yards and his first touchdown of the season as the Rams won 27–9. In Week 4 against the Tampa Bay Buccaneers, Gurley rushed five times for 16 yards and two touchdowns and caught seven passes for 54 yards in the 55–40 loss. In Week 5 against the Seattle Seahawks, Gurley rushed 15 times for 51 yards and two touchdowns in the 30–29 loss. At the midpoint of the season (through eight games), Gurley was tied for 29th in the NFL in rushing yards, in contrast to 2018 when he was the leader, and 2017 when he was fourth. In Week 11 against the Chicago Bears on Sunday Night Football, Gurley rushed 25 times for 97 yards and a touchdown and caught three passes for 36 yards in the 17–7 win. Overall, Gurley finished the 2019 season with 857 rushing yards and 12 rushing touchdowns to go along with 31 receptions for 207 receiving yards and two receiving touchdowns. On March 19, 2020, Gurley was released.

On April 6, 2020, Gurley signed a one-year, US$5.5 million contract with the Atlanta Falcons. The deal included a $2 million signing bonus, as well as $500,000 in incentives if he has 13 touchdowns or 1,000 rushing yards.