Crowell attended George Washington Carver High School in Columbus, Georgia, where he played football and ran track. During his career he rushed for 4,872 yards with 61 touchdowns in 429 carries. He was considered the No. 1 running back recruit by Scout.com and the fourth best by Rivals.com . 
Also a standout track & field athlete, Crowell lettered all four years competing as a sprinter and long-distance runner. He won the 100-meter dash event at the 2009 MCSD Meet, recording a career-best time of 10.91 seconds.  He posted career-bests of 22.38 in the 200m, 52.53 in the 400m and 12:36.84 in the 3200 meter-run. 
With starting running back Washaun Ealey transferring to Jacksonville State in the spring, this led to a vacancy at that position for the 2011 season at the University of Georgia. Second string running back Caleb King was next in line to take over as the team's starting running back, but the senior was declared academically ineligible on July 8.  The position was wide open during football practices in August and leading up to Georgia's opening game at the Georgia Dome against Boise State on September 3. Newcomer Isaiah Crowell earned the starting running back job for the Bulldogs as a freshman for their September 17 game against Coastal Carolina.  However, it was his fine performance against South Carolina on September 10 that created Crowell's chance to take over the starting role as tailback for the University of Georgia as the 6-0, 215-pound true freshman scored two touchdowns while rushing 16 times for 118 yards and catching two passes for 40 yards against the Gamecocks in a 45-42 heartbreaking loss to coach Steve Spurrier's South Carolina Gamecocks  Against Coastal Carolina, Crowell had 16 rushes for 86 yards and highlighted his performance with a 27-yard touchdown run to open the game as Georgia went on to defeat the Chanticleers 59-0. He also had a 12-yard reception in the contest. 
After starting off 0-2, coach Mark Richt's Georgia Bulldogs went on a 10-game winning streak and a first-place ranking in the SEC East, which placed UGA in the SEC Championship Game on December 3. Georgia had a 10-2 record as the AP College Football Poll ranked the Bulldogs No. 12 in the country. 
During the season, Crowell had some breakout performances, such as his 30 carries, 147 yard-outing against Ole Miss on September 24 in Oxford, Mississippi as Georgia won 27-13.  Crowell followed up the Ole Miss performance with 104 yards rushing against Mississippi State on October 1 as Georgia defeated the MSU Bulldogs, 24-10.  He apparently had scored on a 49-yard touchdown run in the contest, but that play was cut short to only 14 yards after the line judge had determined that Crowell's shoe had just touched the sideline — it appeared to be very close according to video replay.  On October 8 at Knoxville, Tenn., Crowell ran into a stout Tennessee defense as he scored two touchdowns but was contained to 19 rushes for 58 yards and two receptions for five yards. Georgia defeated Tennessee 20-12. 
Later in the season on October 29, Crowell helped Georgia win a slugfest against rival Florida 24-20 as the true freshman ran with the football 18 times for 81 yards.  Crowell had another breakout performance – this one against Auburn as he rushed 24 times for 132 yards and a touchdown on November 12 as Georgia won big 45-7. He also caught a pass for one yard against the Tigers. 
An injury slowed Crowell down near the end of the regular season as he suffered a high ankle sprain on November 19 against Kentucky as the running back finished with two rushes for 11 yards. Georgia defeated the Wildcats 19-10.  This caused Crowell to miss the regular-season finale with in-state rival Georgia Tech on November 26.
Georgia played nationally ranked No. 1 LSU (12–0) in the SEC Championship Game on December 3 as Crowell and the Bulldogs would go on to take a 10-0 lead and go into the locker room at halftime up 10-7. He struggled to get on track against the tough Tiger defense as Crowell finished with 10 rushes for 15 yards and a catch for negative three yards. LSU, led by defensive back-punt returner Tyrann Mathieu, exploded in the second half as the Tigers won the contest, 42-10. 
Crowell finished the season with 185 carries for 850 rushing yards and five touchdowns. He also had eight receptions for 59 yards and a touchdown in 12 games.  On December 5, Crowell was named freshman of the year by The Associated Press.  The Georgia Bulldogs were invited to play No. 12 nationally ranked Michigan State (10-3) in the Outback Bowl in Tampa, Fla. on January 2. Georgia lost the game in the third overtime 33-30 and fell to 10-4.
On June 29, Crowell was arrested on felony weapons charges, possession of a weapon in a school zone and possession of a firearm with an altered identification, and the misdemeanor charge of 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 season as the Hornets' leading rusher while helping Alabama State complete 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 30-23. Crowell had five 100-yard rushing games in 2013. After the 2013 season, Crowell declared for the 2014 NFL Draft. He finished 20th in the 2013 Walter Payton Award Voting. 
In July 2016, he posted a controversial image of a faceless person dressed in black, slitting the throat of a captive law enforcement officer, with a knife on his Instagram and later apologized.   
On May 10, 2014, Crowell signed as an undrafted free agent with the Cleveland Browns and was given a $10,000 signing bonus immediately.  Crowell debuted in week one for the Browns as the third-string running back, and rushed for 32 yards and two touchdowns in a loss to the Pittsburgh Steelers.
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. His best performance came in week 12 against the Atlanta Falcons where he rushed for 88 yards on 12 carries with two touchdowns.