Gurley attended Tarboro High School in Tarboro, North Carolina, where he was a three-sport star in football, track and basketball. He played as a running back and defensive back 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 totalling 2,600 yards and 38 touchdowns. Gurley helped his team win the 2A North Carolina state championship, rushing for 242 yards and four touchdowns in the championship game against Northside High School. In the semifinals, Northside had shut down the state's leading rusher, Northside's Shaquan Johnson, who entered the game with 3,083 rushing yards.
Gurley began his freshman season backing up redshirt sophomore Ken Malcome. In his first career game he rushed for 100 yards on eight carries with two touchdowns and also returned a 100-yard kickoff return for a touchdown. Gurley took over as the starter the second game of the season and rushed for 65 yards on 10 carries.
Overall Gurley started 12 of 14 games and rushed for 1,385 yards on 222 carries with 17 touchdowns. Against Georgia Southern, Gurley became the second true freshman in Georgia history to rush for 1,000 yards, the only other being Herschel Walker in 1980. 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 in 2012, the other being T. J. Yeldon of Alabama.
In Georgia's season opener (which was played on August 31) at Clemson's Memorial Stadium, Gurley led the Bulldogs with 154 rushing yards, a career high, on 12 carries and 2 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 10 games, he rushed for 989 yards on 165 carries with 10 touchdowns. After the season, Gurley was named Second-Team All-SEC by the Associated Press.
In the spring of 2013, Gurley joined the Georgia Bulldogs indoor track team. He competed in the 60-meter hurdles, and recorded the seventh-fastest time in school history at 8.12 seconds, to take sixth at the VT Elite Meet.
On October 9, 2014, Gurley was indefinitely suspended by the University of Georgia over Gurley's alleged violation of NCAA rules. It was reported by The Atlanta Journal-Constitution on October 10, 2014, that the impending investigation could have cost Gurley his season. However, it was reported on October 29 that Gurley would sit out two more games until the suspension will be lifted, which made him eligible to play against Auburn. In his first game back from suspension in November, Gurley tore his ACL, ending his junior season. He finished the year with 911 rushing yards and nine touchdowns.
Gurley was drafted 10th overall by the St. Louis Rams in the 2015 NFL Draft. Gurley's rehabilitation went ahead of schedule and during the team's preseason, while he did not play, he practiced without pads on. Soon after, Gurley was medically cleared for full contact by St. Louis team physicians. On Sept 27, 2015, he made his NFL debut against the Pittsburgh Steelers. He was eased into action and finished the game with 6 rushes for 9 yards. The following week, the Rams visited undefeated Arizona for an NFC west divisional matchup. Again Gurley started slow with just 2 yards at halftime, but rushed for 144 yards in the second half as the Rams edged the Cardinals 24-22. The next three games against the Packers, Browns, and 49ers would see Gurley rush for at least 128 rushing yards per game. He scored his first NFL touchdown on Oct 25th, 2015 against the Cleveland 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. 
In Week 9, Gurley was held to just 89 yards in the Rams' 21-18 overtime loss at Minnesota. In Week 10, Gurley was contained to just 49 rushing yards in the Rams 37-13 loss to the Bears. In Week 11, Gurley rushed for 66 yards in the Rams vs Ravens game and scored 1 touchdown in the team's 13-16 loss. In Week 12, Gurley ran just 19 yards in the Rams 7-31 loss to the Bengals. The following week, he was held to just 41 rushing yards on 9 carries in a blowout loss at home against Arizona. In Week 14, Gurley rushed 140 yards in the Rams 14-21 win over the Detroit Lions. In Week 15, Gurley rushed for 48 yards, scored a touchdown and became the third rookie in Rams history to rush for 1,000 yards in a season after Jerome Bettis and Eric Dickerson in the Rams 31-23 victory over the Buccanneers (in what was the franchise's final home game in St. Louis before moving to Los Angeles for the 2016 season) In Week 16, Gurley rushed for 85 yards in the Rams 23-17 victory over the Seattle Seahawks and becoming the second Rams rookie to rush for 1,000 yards and 10 touchdowns since Eric Dickerson in 1983.