San Francisco 49ers 2021 season Mitchell was selected by the
San Francisco 49ers in the sixth round, 194th overall, of the
2021 NFL draft. He signed his four-year rookie contract on May 13, 2021. Mitchell made his NFL debut in the season-opening 41–33 road victory over the
Detroit Lions, finishing with 19 carries for 104 yards and a touchdown. During a Week 7 30–18 loss to the
Indianapolis Colts, he had 18 carries for 107 yards and a touchdown. In the next game against the
Chicago Bears, Mitchell rushed 18 times for 137 yards and a touchdown in the 33–22 road victory. During a Week 12 34–26 victory over the
Minnesota Vikings, he recorded 27 carries for 133 yards and a touchdown. During a Week 17 23–7 victory over the
Houston Texans, Mitchell had 21 carries for 119 yards to go along with two receptions for 11 yards and a touchdown. He also broke the 49ers' single-season rookie rushing record, rushing for 878 yards in 10 games and surpassing
Vic Washington's record 811 yards in 14 games from the
1971 season. Mitchell finished his rookie year with 207 carries for 963 yards and five touchdowns to go along with 19 receptions for 137 yards and a touchdown in 11 games and 10 starts. During the
Wild Card Round against the
Dallas Cowboys, he had 27 carries for 96 yards and a touchdown in the 23–17 road victory. In the
Divisional Round against the
Green Bay Packers, Mitchell had 17 carries for 53 yards during the 13–10 road victory. During the
NFC Championship Game against the
Los Angeles Rams, he recorded three receptions for 50 yards in the 20–17 loss.
2022 season On September 13, 2022, Mitchell was placed on
injured reserve after suffering a sprained MCL in Week 1. He was activated on November 12. Mitchell suffered an MCL tear in Week 12 and was placed on injured reserve on December 3. He was activated on January 7, 2023. In the 2022 season, Mitchell appeared in five games (one start) and had 45 carries for 279 yards and two touchdowns, which both came in the regular-season finale against the
Arizona Cardinals. He finished the 38–13 victory with five carries for 55 yards and the two aforementioned touchdowns. During the
Wild Card Round against the
Seattle Seahawks, Mitchell recorded two receptions for 25 yards and a touchdown in the 41–23 victory. In the
Divisional Round against the Cowboys, he had 14 carries for 51 yards during the 19–12 victory.
2023 season In the 2023 season, Mitchell appeared in 11 games (one start) and recorded 75 carries for 281 yards and two touchdowns, both coming in the last two weeks of the regular season. During the
NFC Championship Game against the
Detroit Lions, Mitchell had four carries for seven yards and a touchdown in the 34–31 comeback victory to help the 49ers reach
Super Bowl LVIII. In the Super Bowl, he rushed twice for eight yards during the 25–22 overtime loss to the
Kansas City Chiefs.
2024 season Mitchell suffered a hamstring injury and was put on season-ending injured reserve on August 27, 2024.
Kansas City Chiefs On March 13, 2025, Mitchell signed a one-year contract with the
Kansas City Chiefs. He only played in one game before being released on December 20.
New England Patriots On December 23, 2025, Mitchell was signed to the
New England Patriots' practice squad. He was released by New England on January 14, 2026. On February 11, Mitchell signed a reserve/futures contract with the Patriots. On April 28, 2026, Mitchell was released by the Patriots. == NFL career statistics ==