During Monday Night Football against the Detroit Lions in Week 1, Crowell finished with 102 rushing yards and two rushing touchdowns, of which one was a 62-yard run, as the Jets won 48–17. Crowell returned to Cleveland for a Thursday Night Football contest in Week 3. He had 16 carries for 34 yards and two rushing touchdowns in the loss to the Cleveland Browns. After running for one of his touchdowns, he used the football to simulate cleaning himself after defecation, then threw the ball into the stands, drawing an unsportsmanlike conduct penalty. With NFL Network carrying the game nationally and Joe Buck on the call, the gesture drew comparisons to when Randy Moss pretended to moon Green Bay Packers fans at Lambeau Field during an NFC Divisional Playoff game in early 2005. Buck had called Moss’ act “disgusting” on air, but was more reserved for Crowell’s celebration. During Week 5 against the Denver Broncos, Crowell finished with 219 rushing yards, including a 77-yard touchdown run as the Jets won 34–16. His 219 rushing yards set a new Jets franchise record. Crowell was awarded AFC Offensive Player of the Week honors for his performance. He was placed on injured reserve on December 14, 2018 with a toe injury he suffered against the Buffalo Bills. He finished the 2018 season with 143 carries for 685 rushing yards and six rushing touchdowns along with 21 receptions for 152 yards.

On June 29, 2012, Crowell was arrested on possession of a weapon in a school zone, possession of a firearm with an altered identification, and carrying a concealed firearm. Crowell was dismissed from the University of Georgia football team due to his arrest and his constant disciplinary problems—including failing a drug test.

During the 2012 season, Crowell ran the ball well, having several good games for Alabama State, including the breakout performance he displayed on September 29 by rushing for 127 yards, which included a 61-yard touchdown run in a 54–14 win against Alcorn State. He finished the 2012 season as the Hornets’ leading rusher while helping Alabama State to a 7–4 record.

In the 2013 season, Crowell helped lead Alabama State to an 8–4 record, good for third place in the SWAC East Division. He finished the year with 1,121 yards rushing and 15 touchdowns. His best game that season came against Jackson State, where he rushed 18 times for 179 yards (averaging 9.9 yards a carry) and a touchdown. However, Alabama State lost to the Jackson State Tigers by a score of 30–23. Crowell had five 100-yard rushing games in the 2013 season. After the 2013 season, Crowell declared for the 2014 NFL Draft. He finished 20th in the 2013 Walter Payton Award Voting.

Despite being projected to be selected as high as the fourth round, Crowell did not get drafted. On May 10, 2014, he signed as an undrafted free agent with the Cleveland Browns and was given a $10,000 signing bonus immediately.

On September 7, 2014, Crowell made his NFL debut, running for 32 yards on 5 carries and two touchdowns in a 30–27 loss to the Pittsburgh Steelers. On September 14, 2014, Crowell ran for 54 yards on 11 carries in a win over the New Orleans Saints, the Browns’ first home opening win in a decade. On September 21, 2014, Crowell scored his third touchdown of the season against the Baltimore Ravens. Crowell and rookie running back Terrence West each scored a rushing touchdown, the first time two Browns rookies had done that in a single game since 1979 (Dino Hall and Pat Moriarty). On October 12, 2014, Crowell ran for 77 yards on 11 carries and a touchdown against the Pittsburgh Steelers. On November 6, 2014, Crowell scored his 4th touchdown of the season against the Cincinnati Bengals. On November 16, 2014, Crowell ran for 61 yards on 14 carries against the Houston Texans. On November 23, 2014, Crowell ran for a season-high 88 yards on 12 carries and two touchdowns against the Atlanta Falcons. On December 7, 2014, Crowell scored his eighth touchdown of the season against the Indianapolis Colts. He finished the season playing 16 games for 607 rushing yards on 148 attempts (4.1 yards per attempt) and 8 touchdowns plus 9 receptions for 87 yards while starting 4 games. Among rookies, Crowell ranks fifth in rushing yards, only one of nine rookies to break 500 yards, and one of five to break 600 yards. Crowell was ranked second in rushing touchdowns among rookies, just behind Cincinnati Bengals’ running back Jeremy Hill.

On September 20, 2015, Crowell ran for 72 yards on 15 carries and a touchdown against the Tennessee Titans. On October 4, Crowell ran for 63 yards on 12 carries against the San Diego Chargers, including a 32-yard run. Crowell recorded a career-high 62 receiving yards, including a career-long 53-yard catch. Crowell recorded 125 total yards and running back Duke Johnson recorded 116 total yards as well, this marked the first time the Browns had two running backs each record more than 100 total yards in the same game since 2004 (Lee Suggs with 119 yards and William Green with 115). On October 11, Crowell scored his first touchdown reception of his career against the Baltimore Ravens. On December 6, Crowell ran for 62 yards on 11 carries against the Cincinnati Bengals. On December 13, Crowell ran for 145 yards on 20 carries and 2 touchdowns against the San Francisco 49ers. Included, Crowell had a 50-yard run. Crowell was the Browns’ first 100-yard rusher of the season. On December 27, Crowell ran for 88 yards on 16 carries and a touchdown against the Kansas City Chiefs. Crowell finished the 2015 season with 706 rushing yards on 185 carries with 4 touchdowns, averaging 3.8 yards a carry. He played in all 16 games of the season and was the starting running back in nine of those games. Among second-year running backs, Crowell ranked third in rushing yards, only behind Devonta Freeman of the Atlanta Falcons and Jeremy Hill of the Cincinnati Bengals. In the 2015 season, Crowell did not have a fumble.

On September 11, 2016, Crowell ran for 62 yards on 12 carries and a touchdown in the season opener against the Philadelphia Eagles. On September 18, versus the Baltimore Ravens, Crowell recorded a career-long 85-yard touchdown run. The run was the second-longest rushing play in franchise history, behind Bobby Mitchell’s 90-yard run in 1959. He finished the game with 133 yards on 18 carries and a touchdown, averaging 7.4 yards per carry. On September 25, Crowell ran for 79 yards on 15 carries against the Miami Dolphins, including a 25-yard run. Crowell ran for three straight games with at a rushing average of at least five yards per carry for Crowell, a first in his career. On October 2, Crowell ran for 112 yards on 16 carries and a touchdown against the Washington Redskins. Crowell’s 386 yards were the most by a Brown through the first four games of a season since Jim Brown recorded 476 yards in 1965. On October 23, Crowell ran for 63 yards on 12 carries and a touchdown against the Cincinnati Bengals. On October 30, Crowell scored his fifth touchdown of the season against the New York Jets. Crowell finished the 2016 season with a career-high 952 rushing yards and 319 receiving yards. His 4.8 yards per carry ranked fifteenth among NFL running backs in the 2016 season.

In July 2016, following the deaths of Alton Sterling and Philando Castile, Crowell posted on his Instagram a controversial violent image of a faceless person dressed in black who was slitting the throat of a captive law enforcement officer with a knife; he later had the photo deleted and apologized for his actions.

On February 28, 2017, the Browns placed a second-round tender on Crowell, keeping him in Cleveland through 2017.

In the season opener, Crowell had 33 rushing yards, 33 receiving yards, and a two-point conversion in the 21–18 loss to the Pittsburgh Steelers. In Week 5, a 17–14 loss to the New York Jets, he had his best rushing game of the season to that point with 60 yards. In Week 8 against the Minnesota Vikings, he had 64 rushing yards and his first rushing touchdown of the season. In the next game, against the Detroit Lions, he had 90 rushing yards and a touchdown in the 38–24 loss. On November 26, in a loss to the Cincinnati Bengals, he had 95 rushing yards. On December 10, in an overtime loss to the Green Bay Packers, he finished with a season-high 121 rushing yards. Overall, in the 2017 season, he finished with 853 rushing yards, two rushing touchdowns, 28 receptions, and 182 receiving yards as the Browns recorded the second 0–16 season in NFL history.

On March 14, 2018, Crowell signed a three-year deal worth $12 million with the New York Jets.

On March 14, 2019, Crowell was released by the Jets, after they signed Le’Veon Bell in free agency.

On March 28, 2019, Crowell signed a one-year contract with the Oakland Raiders. On April 29, he suffered a torn Achilles during a team workout. He was placed on injured reserve on May 3, 2019, ending his season.