He played college football for the Stanford Cardinal and was selected by the Carolina Panthers eighth overall in the 2017 NFL draft.

As a sophomore in 2015, McCaffrey was named AP College Football Player of the Year and was a finalist for the Heisman Trophy.

McCaffrey was traded to the 49ers in 2022 and was named the 2023 Offensive Player of the Year after leading the league in scrimmage yards and touchdowns en route to an NFC Championship and appearance in Super Bowl LVIII.

A member of the McCaffrey football family, he is the son of Ed and brother of Max, Dylan, and Luke.

[7] Considered one of the best one hundred football players in his national high school class, he was selected as a 2014 U.S. Army All-American.

[28] After being injured during the Cardinal's 42–16 loss to Washington State on October 8, McCaffrey sat out for the team's 17–10 victory in the 2016 edition of the Notre Dame-Stanford rivalry the following week.

He attended Stanford's Pro Day, but was satisfied with his combine numbers and only ran positional drills for the NFL scouts and representatives.

[52] In Week 5 against the Detroit Lions, McCaffrey scored his first career touchdown on a six-yard shovel pass from quarterback Cam Newton.

[54] In the team's Monday Night Football win over the Miami Dolphins, McCaffrey scored twice–one rushing and one receiving–and totaled 50 yards.

[55] In Week 15, in a victory over the Green Bay Packers, McCaffrey brought his season total to 73 catches and five receiving touchdowns, being the only rookie running back in NFL history with at least 70 receptions and five touchdown catches before being joined by Alvin Kamara later in the season.

[56][57] The following week, against the Tampa Bay Buccaneers, McCaffrey brought his catch total to 75, breaking the Panthers rookie record of 74 set by Kelvin Benjamin.

[64] Though limited in yardage for much of the middle of the season, from Weeks 8–10 McCaffrey compiled seven touchdowns in three games (joining DeAngelo Williams in 2008 as the only other Panther with this distinction), including all of Carolina's scores in a 52–21 loss to the Pittsburgh Steelers.

[67] During Week 15, in a Monday Night Football showdown against the 11–2 Saints, McCaffrey threw a 50-yard touchdown pass on 4th and 2 to Chris Manhertz.

[70] Since the Panthers were eliminated from the playoffs, he had a limited role in the Week 17 victory over the New Orleans Saints with 40 total yards.

[72] McCaffrey had the opposite of a sophomore slump, as he became the Panthers franchise record holder of all-purpose yards in a season with 1,965.

[74] Michael Thomas also broke Centers' record in 2018, catching 85.0% of his targets while playing for the New Orleans Saints.

He also fumbled for the first time this season, and was stopped just short of the goal line in a failed comeback late in the fourth quarter in the 16–24 loss.

During the game, McCaffrey joined Roger Craig and Marshall Faulk as the only players to have 1,000 yards rushing and receiving in the same season.

[94] He accounted for 43% of his team's offensive yards during the season, the largest percentage of any individual player in the NFL.

[96] On April 16, 2020, McCaffrey signed a four-year, $64 million contract extension with the Panthers through the 2025 season, making him the highest-paid running back in NFL history.

[100] When McCaffrey rushed for his second touchdown early in the fourth quarter, he suffered a high ankle sprain and missed the rest of the game.

[118] In Week 8 against the Rams, McCaffrey became the first 49ers running back to record passing, rushing, and receiving touchdowns in the same game.

In the Wild Card Round against the Seattle Seahawks, he had 15 carries for 119 rushing yards to go with a receiving touchdown in the 41–23 victory.

[145] McCaffrey won his first Offensive Player of the Year award and finished third in NFL MVP voting, behind quarterbacks Dak Prescott and Lamar Jackson.

[153] After head coach Kyle Shanahan stated that McCaffrey had his worst day in terms of pain during practice leading up to Week 2, the 49ers placed him on injured reserve.

[159] Following the game, Shanahan stated the injury has an expected six-week recovery period and that he would be placed on IR, ending his regular season.

His older brother Max played football at Duke University, and then on several NFL teams as a wide receiver.

[179][180] His maternal grandfather Dave Sime (1936–2016) was a pioneering ophthalmologist and an Olympic sprinter,[181] the silver medalist (photo finish) in the 100 meters in 1960.

When you have a bunch of people chanting your name, it's important that you give the honor and glory back to the person, God, that's allowing me to do this.

[187] In 2018, McCaffrey appeared on a commercial for the NFL, along with Jay Ajayi, Todd Gurley, and DeAndre Hopkins.