He played college football at Nebraska, and was selected by the Cincinnati Bengals in the sixth round of the 2013 NFL draft.

After spending the 2023 NFL season as an un-signed free agent, Burkhead announced his retirement from professional football during the 2024 off-season.

[1] As a junior, he rushed for 1,762 yards and 28 touchdowns, leading the school to a state semifinal appearance in the Texas 5-A football playoffs.

[10][11][12] He was considered the ninth or tenth best running back prospect for the 2013 NFL draft and was ranked in the top 150 overall.

He earned repeated scholar-athlete awards throughout his career, including first-team CoSIDA Academic All-American in 2011 and 2012, and recognition as one of 15 National Football Foundation Scholar Athletes in 2012.

[15] After being selected by the Cincinnati Bengals in the sixth round of the 2013 NFL draft with the 190th overall pick, he signed with the team on May 13, 2013.

[23] In 2016, Burkhead appeared in all 16 regular season games for the Bengals, including one start at running back.

[28] On September 17, against the New Orleans Saints in Week 2, he recorded his first touchdown as a member of the Patriots when he hauled in a 19-yard pass from quarterback Tom Brady in the first quarter of the 36–20 victory.

[35] In Week 3 against the Detroit Lions, Burkhead suffered a neck injury and was placed on injured reserve on September 26, 2018.

[38] On January 13, 2019, Burkhead scored his first-ever postseason touchdown in the Divisional Round with a six-yard run against the Los Angeles Chargers in a game New England won 41–28.

One week later, he scored the game-winning touchdown in overtime as part of the 2019 AFC Championship game against the Kansas City Chiefs.

[40] During the Super Bowl, Burkhead finished with 43 rushing yards, had the longest rushing play of the game (26 yards, tied with Sony Michel), and led all running backs from both teams with a 6.1 yards-per-carry average, as the Patriots defeated the Los Angeles Rams by a score of 13–3 in the lowest-scoring Super Bowl in history.

[41] In New England's three playoff games, Burkhead totaled seven receptions on seven targets for 45 yards and registered one tackle on special teams.

[49] In Week 16, against the Los Angeles Chargers, Burkhead finished the game with a career high 149 rushing yards along with two touchdowns in the 41–29 victory.

He was awarded for his work with a 6-year-old suffering from a rare pediatric brain tumor called a low-grade glioma.

[57] Burkhead's commitment to community service has been personified by his friendship with that child, Jack Hoffman, a cancer patient from Atkinson, Nebraska.