In the season opener, against the Atlanta Falcons, he finished with 60 rushing yards and two rushing touchdowns in the 37–34 overtime loss. In the next game, a 26–24 loss to the Cleveland Browns, he finished with 83 rushing yards and his third rushing touchdown of the season. On October 26, Ingram ran for a career-high 172 yards on 24 carries and added one touchdown as the Saints defeated the Green Bay Packers 44–23. With his 30 carry, 100 yard and 2 touchdown performance against the Carolina Panthers in the Saints’ next game, Ingram became the first Saint since Deuce McAllister in 2006 to rush for over 100 yards in consecutive games. In the next game against the San Francisco 49ers, he finished with 120 rushing yards. After a 67-yard game against the Cincinnati Bengals and a 27-yard game against the Baltimore Ravens, he had 122 rushing yards against the Pittsburgh Steelers. In the last three games of the regular season, he finished with a rushing touchdown in each game. He finished the 2014 NFL season with a career-high 1,109 yards from scrimmage (964 rushing yards and 145 receiving yards).

In the season opener against the Oakland Raiders, Ingram finished with 58 rushing yards and 29 receiving yards. After a 30-yard game against the New York Giants and a 77-yard game against the Atlanta Falcons, he had 56 rushing yards and his first touchdown of the season against the San Diego Chargers. On November 6, against the San Francisco 49ers, he finished with 158 rushing yards and a touchdown. In Week 12 of the 2016 season, Ingram ran for 146 yards on 14 attempts and a touchdown along with one catch for 21 yards for a touchdown in a 49–21 win against the Los Angeles Rams, earning him NFC Offensive Player of the Week. Five weeks later, against the Atlanta Falcons, Ingram rushed for 103 yards on 20 attempts becoming the Saints’ first 1,000 yard rusher since Deuce McAllister in 2006 over a decade earlier. He finished the season with a career-high 1,043 rushing yards and added an additional 319 receiving yards to go along with 10 total touchdowns. Ingram’s 5.1 yards per attempt ranked ninth among NFL running backs in 2016.

Considered a four-star recruit by Rivals.com, Ingram was listed as the No. 17 high school athlete in the nation in 2008.

Ingram played behind Glen Coffee his freshman year, and he was selected to the 2008 SEC All-Freshman Team. He made his collegiate debut in the season opener against Clemson. In the victory over the Tigers, he finished with 17 carries for 96 yards. In the next game against Tulane, he recorded his first collegiate rushing touchdown. He followed that up with 51 rushing yards and two more rushing touchdowns in a victory over Western Kentucky in the next game. In his first conference game against the Arkansas Razorbacks, he had 53 rushing yards and a touchdown. In the next game against Georgia, he was limited to 17 yards but had his fourth straight game with a rushing touchdown. After a 66-yard performance against Kentucky, he had 73 rushing yards and a touchdown against Ole Miss. On October 1, against Arkansas State, he finished with 113 rushing yards and two rushing touchdowns. On October 15, against Mississippi State, he finished with 78 rushing yards and a touchdown. In the Iron Bowl, against Auburn, he finished with 64 rushing yards, two rushing touchdowns, and 27 receiving yards. In the SEC Championship against Florida, he was held to 21 rushing yards but had a rushing touchdown. In the Sugar Bowl, against Utah, he finished the season with 26 rushing yards. Overall, in the 2008 season, he finished with 728 rushing yards and 12 rushing touchdowns. His team-high 12 touchdowns also set the Alabama freshman school record.

In the 2009 SEC Championship Game versus the undefeated and top-ranked Florida Gators, Ingram rushed for 113 yards and three touchdowns, while also catching two passes for 76 receiving yards to combine for 189 all-purpose yards. In the game, Ingram also surpassed Bobby Humphrey’s single-season rushing record for the Crimson Tide, reaching 1,542 rushing yards for the season.

On January 7, 2010, Alabama defeated Texas 37–21 to win the BCS National Championship. Ingram received honors as Offensive MVP after rushing for 116 yards and two touchdowns on 22 carries. For the 2009 season, Ingram rushed for 1,658 yards and 17 touchdowns, and also had 334 receiving yards with 3 touchdowns.

Ingram finished his junior season with 875 yards on 158 carries with 13 touchdowns, with an additional 282 yards receiving and a touchdown. On January 6, 2011, Ingram announced he would forgo his senior season and enter the 2011 NFL Draft. At the time of the announcement, he was projected as a first round pick.

The New Orleans Saints selected Ingram in the first round with the 28th pick in the 2011 NFL Draft—the same pick number the Giants used to draft his father, Mark Ingram Sr., twenty-four years earlier, at the same age. Ingram was the first running back drafted in 2011; since the 1970 AFL-NFL merger, this was the latest pick used for the first running back chosen in an NFL draft. The Saints acquired the pick from the New England Patriots, trading their second-round selection (#56 overall) and their first-round selection in 2012 to do so. As Alabama head coach Nick Saban is part of Patriots head coach Bill Belichick’s coaching tree, the Patriots were widely assumed to be interested in drafting Ingram themselves. On July 28, 2011, Ingram decided on the number #28 in honor of his and his father’s draft pick number. The next day Ingram agreed with the Saints on a four-year contract, with three years guaranteed and a fifth year option. The contract is worth $7.41 million, with a $3.89 million signing bonus.

On August 12, 2011, Ingram scored his first career touchdown as a Saint on a 14-yard run in a preseason game against the San Francisco 49ers. On September 25, Ingram scored his first touchdown in regular season play as a Saint on a tough 13-yard run against the Houston Texans. On October 23, late in the game on Sunday Night Football in a runaway win against the Indianapolis Colts Ingram injured his heel. It was considered a ‘day-to-day’ injury at first, but Ingram was unable to practice the entire week and missed the following game versus the winless St. Louis Rams which ended in a 31–21 loss for the Saints. He returned to action against the Atlanta Falcons on November 13. On November 28, against the New York Giants, he finished with 80 rushing yards and a touchdown. In his final action of the 2011 season on December 4, he finished with 54 rushing yards and a touchdown against the Detroit Lions. He suffered a toe injury and missed the remainder of the season. He finished his rookie season with 474 rushing yards and five touchdowns.

Ingram remained in the Saints’ backfield for the 2012 season. He had 15 rushing yards in a season opening loss to the Washington Redskins. In Week 2, against the Carolina Panthers, he finished with 53 rushing yards and his first touchdown of the season. Through Week 10, his best outing was 67 rushing yards in a 31–27 victory over the Atlanta Falcons. In the following game, against the Oakland Raiders, he finished with 67 rushing yards and a touchdown. On November 29, he was limited to only 13 yards but had one touchdown in the 23–13 loss to the Falcons. In Week 15, he had his best outing of the season with 90 rushing yards and a touchdown in a 41–0 win over the Tampa Bay Buccaneers. In the penultimate game of the season, he finished with 53 rushing yards and a touchdown against the Dallas Cowboys. Overall, in the 2012 season, he finished with 602 rushing yards and five rushing touchdowns.

After wearing the #28 jersey for two seasons, Ingram changed to number 22, the number he wore at Alabama, before the beginning of the 2013 season. He started off the season slow with only 31 combined rushing yards in the first two games. Ingram’s performance was hampered by a toe injury. He returned to action on November 3, but only posted 19 rushing yards against the New York Jets. In the next game, a 49–17 win over the Dallas Cowboys, he had a career day with 145 rushing yards and a touchdown. Over the remainder of the season, he did not post over 32 rushing yards in a single game barring the Week 16 game against the Carolina Panthers, where he had 83 yards. Overall, in the 2013 season, he finished with 386 rushing yards and one rushing touchdown. The Saints qualified for the playoffs in the 2013 season. In the Wild Card Round against the Philadelphia Eagles, he finished with 97 rushing yards, one rushing touchdown, and 17 receiving yards in the 26–24 victory. In the Divisional Round against the Seattle Seahawks, he finished with 49 rushing yards in the 23–15 loss.

On March 7, 2015, Ingram and the Saints agreed to a four-year deal. In the season opener against the Arizona Cardinals, he was held to 24 rushing yards in the 31–19 loss. In the next game, a loss to the Tampa Bay Buccaneers, he finished with 53 rushing yards and his first touchdown of the season. He scored another rushing touchdown in the next game against the Carolina Panthers. On October 15, against the Atlanta Falcons, he finished with 46 rushing yards and two rushing touchdowns. In the next game, a 27–21 victory over the Indianapolis Colts, he had his best game of the season with 143 rushing yards and a touchdown. On November 15, Ingram injured his shoulder in the Week 10 matchup against the Washington Redskins. Ingram and the Saints would end up losing the game 47 to 14. On December 6, against the Carolina Panthers, he made his final appearance of the season and had 56 rushing yards and a touchdown. He finished the 2015 season with 769 rushing yards, six rushing touchdowns, and 405 receiving yards.

Mark Ingram began the 2017 season sharing carries with former Vikings star Adrian Peterson and rookie Alvin Kamara, but became the team’s first-option rusher in Week 3. After averaging just 42 yards a game through the first four, after the Saints’ bye week Ingram had consecutive 100+ yard games against Detroit and Green Bay in Weeks 6 and 7, including his first three touchdowns of the season. In Week 10, he led the NFL with 131 rushing yards and his first career game with three touchdowns in an emphatic 47–10 victory over Buffalo, moving him into a three-way tie for the league lead in rushing touchdowns at seven with Ezekiel Elliott and Todd Gurley. In Week 11, he again led the NFL with 134 rushing yards and a touchdown on just 11 carries in a 34–31 overtime win over Washington, earning him NFC Offensive Player of the Week. Kamara also had 100+ yards from scrimmage in both games. In Week 13, he recorded 85 yards rushing and scored his NFL-leading ninth rushing touchdown (trailing only teammate Kamara and Todd Gurley for the lead in total touchdowns; they had 11 each). On December 19, 2017, Ingram was named to his second Pro Bowl alongside Kamara, becoming the first ever pair of running backs from the same team to earn the honors. He finished the regular season with career-highs of 1,124 rushing yards, 12 rushing touchdowns, 58 receptions, and 416 receiving yards. He finished sixth in the league in rushing yards, and second in rushing touchdowns behind Todd Gurley. Ingram and Kamara became the first running back duo in NFL history to each have over 1,500 scrimmage yards in the same season. The Saints won the NFC South in the 2017 season. In the Wild Card Round, against the Carolina Panthers, Ingram finished with 22 rushing yards and 13 receiving yards in the 31–26 victory. In the Divisional Round against the Minnesota Vikings, he finished with 25 rushing yards in the 29–24 loss. He was ranked 43rd by his fellow players on the NFL Top 100 Players of 2018.

On May 8, 2018, Ingram was suspended for the first four games of the season due to violating the policy on performance-enhancing drugs. He returned in Week 5 and recorded 53 rushing yards and two rushing touchdowns in the 43–19 victory over the Washington Redskins on Monday Night Football. In Week 10 against the Cincinnati Bengals, he had 104 rushing yards, 58 receiving yards, and a receiving touchdown in the 51–14 victory. In Week 11, against the Philadelphia Eagles, he had 103 rushing yards and two rushing touchdowns. In Week 16 against the Pittsburgh Steelers, Ingram recorded his 50th touchdown, surpassing Deuce McAllister for the Saints franchise record for rushing touchdowns. Overall, in the 2018 season, Ingram had 645 rushing yards and six rushing touchdowns to go along with 21 receptions for 170 receiving yards and one receiving touchdown. The Saints won the NFC South and had home-field advantage throughout the NFC Playoffs as the #1-seed. In the Divisional Round against the Philadelphia Eagles, Ingram had 53 rushing yards in the 20–14 victory. In the NFC Championship against the Los Angeles Rams, he had 31 rushing yards in the 26–23 overtime loss.

On March 13, 2019, Ingram signed a three-year, $15 million contract with the Baltimore Ravens. Ingram made his debut with the Ravens in Week 1 against the Miami Dolphins. In the game, Ingram rushed 14 times for 107 yards and two touchdowns as the Ravens won 59-10. In Week 3 against the Kansas City Chiefs, Ingram rushed 16 times for 103 yards and 3 touchdowns as the Ravens lost 33-28. In Week 9 against the New England Patriots, Ingram rushed 15 times for 115 yards and caught two passes for 29 yards in the 37–20 win. In Week 11 against the Houston Texans, Ingram rushed 13 times for 48 yards and caught three passes for 37 yards and two touchdowns in the 41–7 win. In Week 12 against the Los Angeles Rams on Monday Night Football, Ingram rushed 15 times for 111 yards and a touchdown and caught one pass for a seven-yard touchdown in the 45–6 win. In Week 16 against the Cleveland Browns, Ingram rushed eight times for 55 yards and caught two passes for 36 yards and a touchdown before exiting the game due to a calf injury. Without Ingram, the Ravens won 31–15. During the game, Ingram surpassed 1,000 rushing yards on the season. On the season, Ingram finished with 1,018 rushing yards and ten rushing touchdowns to go along with 26 receptions for 247 receiving yards and five receiving touchdowns.