In the second game of the season, against Nevada, Freeman had 109 rushing yards and a touchdown. In the next game against Bethune-Cookman, he had 112 rushing yards and a touchdown. On October 5, against Maryland, he started a streak of ten straight games with a rushing touchdown. On October 26, against North Carolina State, he had 92 rushing yards and two rushing touchdowns. In the next game, against Miami, he had 78 rushing yards and two more rushing touchdowns to go along with 98 receiving yards and receiving touchdown. On November 23, against Idaho, he had 129 rushing yards and a rushing touchdown. As a junior, Freeman was a first-team All-Atlantic Coast Conference (ACC) selection and helped the Florida State Seminoles win the 2014 BCS National Championship Game over Auburn by a score of 34–31. He rushed for over 1,000 yards, the first Seminole to do so since Warrick Dunn in 1996. Freeman finished the season with career highs in rushing yards (1,016), receiving yards (278), and touchdowns (15) despite splitting carries with James Wilder, Jr. and Karlos Williams in Florida State’s backfield. He led the Seminoles in rushing in each of his three seasons in Tallahassee.

Considered a four-star recruit by Rivals.com, he was rated the best running back in the nation. He committed to Florida State on June 24, 2010.

In the second game of his sophomore season, he had 69 rushing yards and a rushing touchdown against Savannah State. On October 20, he had 70 rushing yards and two rushing touchdowns against the Miami Hurricanes. In the next game against Duke, he had 104 rushing yards and two rushing touchdowns. After a forgettable performance against Virginia Tech in which he had −5 rushing yards on seven carries, he had 148 rushing yards and two rushing touchdowns against Maryland. Florida State finished with a 10–2 regular season record and qualified for the conference championship game. In the ACC Championship against Georgia Tech, he had 59 rushing yards and a rushing touchdown in the 21–15 victory. As a sophomore in 2012, he had 111 carries for 660 yards and eight touchdowns.

On January 11, 2014, Freeman announced he would forego his senior season and enter the 2014 NFL Draft.

In his rookie season in 2014, Freeman shared touches with fellow running backs Steven Jackson, Jacquizz Rogers, and Antone Smith. In his NFL debut, against the New Orleans Saints in Week 1 at the Georgia Dome, Freeman had two rushes for 15 yards and two receptions for 18 yards in the 37–34 overtime victory. Against the Detroit Lions in Week 8, he scored his first career touchdown, a seven-yard reception from Matt Ryan in the first quarter. Against the New Orleans Saints in Week 16, he scored his first career rushing touchdown, a 31-yard rush in the third quarter. He appeared in all 16 games during his rookie season but started none. In his rookie season, he accumulated 248 rushing yards on 65 carries, 225 receiving yards on 30 receptions, one rushing touchdown, and two receiving touchdowns.

After recording just 18 rushing yards against the Philadelphia Eagles in the season opener on Monday Night Football and 25 rushing yards against the New York Giants, Freeman received his first career start on September 27, 2015 against the Dallas Cowboys. Against the Cowboys, Freeman had a breakout performance by rushing for a then career-high 141 yards and three touchdowns on 30 carries. The next week, he rushed for three touchdowns again to go along with 68 rushing yards against the Houston Texans. In the following game against the Washington Redskins, he rushed for a career-high 153 yards to start a three-game streak of 100 yard performances from Weeks 4–7. In Week 11 against the Indianapolis Colts, Freeman recorded 43 yards off three carries before leaving in the first half with a concussion. By the end of the season, Freeman totaled 1,634 yards-from-scrimmage (5th in the NFL), 14 all-purpose touchdowns (1st) with 1,056 rushing yards (7th) and 11 rushing touchdowns (1st). He also finished the 2015 season ranked third among NFL running backs in both receptions (73) and receiving yards (578) along with three receiving touchdowns. Following the season, Freeman was selected to the Pro Bowl, the first of his career, and was named a Second-team All-Pro. Freeman was named one of the captains, along with Geno Atkins of the Cincinnati Bengals, for Team Irvin in the 2016 Pro Bowl. He was ranked as the 50th best player in the NFL and the fifth best running back by his fellow players on the NFL Top 100 Players of 2016.

Freeman entered the 2016 season looking to advance on his successful season the year before. Freeman and Tevin Coleman would provide the Falcons with a solid running back combination in 2016. In Week 3, against the New Orleans Saints, he had 14 carries for 155 yards and five receptions for 55 yards and a touchdown. The next week, against the Carolina Panthers, he scored his first rushing touchdown of the season in the 48–33 win. In Week 12, against the Arizona Cardinals, he churned out 60 yards and two touchdowns on 15 carries in the 38–19 victory. In the next game, a 29–28 loss to the Kansas City Chiefs, he had another two-touchdown performance on 15 carries for 56 yards. In Week 15, Freeman ran for 139 yards on 20 carries for three touchdowns in a 41–13 win over the San Francisco 49ers, and was named NFC Offensive Player of the Week. Freeman was named to his second consecutive Pro Bowl as an original selection behind Ezekiel Elliott and David Johnson, and played a huge role in the Falcons finishing with an 11–5 record and earning the #2 seed in the NFC. In the Divisional Round 36–20 victory over the Seattle Seahawks, Freeman had 14 carries for 45 yards and scored his first career postseason touchdown and also recorded four catches for 80 yards. In the NFC Championship 44–21 victory over the Green Bay Packers, Freeman recorded 14 carries for 42 yards and four receptions for 42 yards and scored his first career postseason receiving touchdown. In Super Bowl LI, where the Falcons lost 34–28 in overtime to the New England Patriots, Freeman would have 11 carries for 75 yards, two receptions for 46 yards, and scored the first points for either team on a rushing touchdown in the second quarter. Freeman was ranked as the 41st best player in the NFL and the sixth best running back by his fellow players on the NFL Top 100 Players of 2017.

On August 9, 2017, Freeman signed a five-year, $41.25 million contract extension with the Falcons to become the highest paid running back in the NFL. In Week 1, against the Chicago Bears, he was limited to 37 rushing yards on 12 carries but had a touchdown in the 23–17 victory. In Week 2, in the 34–23 victory over the Green Bay Packers, he had 84 rushing yards and two touchdowns in the first game in the new Mercedes-Benz Stadium. Freeman’s first touchdown was the first ever touchdown in the history of the new stadium. In Week 3, against the Detroit Lions, he recorded 106 rushing yards and a touchdown. Though splitting carries with Tevin Coleman, he scored five rushing touchdowns in the first four games to lead the NFL. In Week 4, against the Buffalo Bills, he had 58 rushing yards and a touchdown for his fourth straight game with at least one in 2017. Over the next six games, Freeman did not record a touchdown. That streak ended on Thursday Night Football in Week 14 against the New Orleans Saints. In the 20–17 victory, he had 24 carries for 91 yards and a touchdown. In the next game, against the Tampa Bay Buccaneers, he had 22 carries for 126 yards and a touchdown in the 24–21 victory on Monday Night Football. In the regular season finale against the Carolina Panthers, he had 23 rushing yards, 85 receiving yards, and a receiving touchdown in the 22–10 victory. The Atlanta Falcons finished with a 10–6 record and made the playoffs. Overall, Freeman finished with 865 rushing yards, seven rushing touchdowns, 36 receptions, 317 receiving yards, and one receiving touchdown in the 2017 season. In the Wild Card Round, against the Los Angeles Rams, he had 66 rushing yards and a rushing touchdown in the 26–13 victory. In the Divisional Round, he had a receiving touchdown in the 15–10 loss to the Philadelphia Eagles. The touchdown marked Freeman’s fifth consecutive postseason game with a touchdown. He was ranked 70th by his peers on the NFL Top 100 Players of 2018.

In Week 1, Freeman suffered a knee injury and missed the next three games. He returned in Week 5 before injuring his foot and experienced soreness in his groin. He missed the following week and was later revealed that Freeman required groin surgery. He was placed on injured reserve on October 16, 2018.

In Week 6 against the Arizona Cardinals, Freeman rushed 19 times for 88 rushing yards and caught three passes for 30 receiving yards and two receiving touchdowns in the 34–33 loss. During Week 7 against the Los Angeles Rams, Freeman threw a punch at Aaron Donald, and was ejected. Without Freeman, the Falcons lost 37–10. In the 2019 season, Freeman finished with 656 rushing yards and two rushing touchdowns to go along with 59 receptions for 410 receiving yards and four receiving touchdowns. The Falcons released Freeman on March 16, 2020.

On September 23, 2020, Freeman signed a one-year, $3 million contract with the New York Giants. In Week 5, against the Dallas Cowboys, he recorded his first rushing touchdown as a Giant in the 37–34 loss. On November 13, 2020, he was placed on injured reserve with an ankle injury.