In 2014, he garnered AFCA first-team All-American honors and was awarded the ACC Player of the Year.

He made his collegiate debut during the Panthers' season opening loss to Florida State and had eight carries for 34 yards.

[10][11] Conner started his sophomore season rushing for 153 yards on 14 carries and scored a season-high four touchdowns in the season-opening 62–0 win over Delaware.

[16][17] At the end of the season, he was named the ACC Player of the Year[18] and garnered American Football Coaches Association first-team All-American honors.

On September 5, 2015, Conner tore his MCL during the Panthers' season opening 45–37 victory over Youngstown State.

[23] On September 17, 2016, Conner had a season-high 24 carries for 111 rushing yards and a touchdown during a 38–45 loss to Oklahoma State.

[25][26] On December 10, 2016, Conner announced via Twitter that he intended to apply for early eligibility for the 2017 NFL draft as an underclassman and forgo his senior year at Pitt.

At the conclusion of the pre-draft process, Conner was projected to be a fifth or sixth round pick by NFL draft scouts and experts.

[33] He had the top selling NFL jersey throughout July, beating all rookies, as well as Marshawn Lynch, Von Miller, Dak Prescott, and Tom Brady.

[35][36] Conner entered training camp competing with veterans Knile Davis and Fitzgerald Toussaint for the vacant backup running back position left by DeAngelo Williams.

Davis and Toussaint were released during final roster cutdowns, and Steelers head coach Mike Tomlin named Conner the backup to Le'Veon Bell to begin the regular season.

[37] Conner made his NFL debut in the season-opener at the Cleveland Browns and had four carries for 11 yards in a 21–18 victory.

On December 19, 2017, he was placed on injured reserve due to an MCL injury that required surgery.

[40] Head coach Mike Tomlin named Conner the starting running back to begin the regular season after Le'Veon Bell's decision to indefinitely hold out due to a contract dispute over a long-term deal.

[41] Conner made his first NFL start in the season-opener at the Browns and had 31 carries for 135 rushing yards and two touchdowns in a 21–21 tie.

[53] In Week 2 against the Seattle Seahawks, Conner injured his knee and exited the game in the third quarter.

[55] In Week 8 against the Miami Dolphins on Monday Night Football, Conner rushed 23 times for 145 yards and a touchdown before exiting the game with a shoulder injury.

[57] Conner made his return from injury in Week 11 against the Browns on Thursday Night Football.

[59] In Week 1 against the New York Giants on Monday Night Football, Conner rushed six times for nine yards before exiting the game due to an ankle injury.

[68] In Week 9, Conner led the Cardinals over the San Francisco 49ers with 173 scrimmage yards and three touchdowns.

"[95] After tearing his MCL during the Panthers' first game of 2015, Conner attended rehab and began experiencing excessive fatigue and other symptoms, leading doctors to perform a chest x-ray that revealed Hodgkin's Lymphoma.

During his treatment, Conner continued to participate in non-contact drills with the Pittsburgh Panthers football team as much as his body would allow.

[96] Conner appeared on the April 21, 2016 episode of The Ellen DeGeneres Show and met Kansas City Chiefs' safety Eric Berry, who also overcame Hodgkin's lymphoma and whom Conner saw as an inspirational figure.

[97] During the 2018 season, Conner began growing a mullet, which became popular among Steeler fans and fully embracing the Yinzer culture with the hairstyle.