Conner attended McDowell High School in Erie, Pennsylvania. He was a running back and defensive lineman. As a senior, he rushed for 1,680 yards on 155 carries and 26 touchdowns. He committed to play college football at the University of Pittsburgh in August 2012.
As a true freshman in 2013, Conner played in 12 of 13 games. He made his collegiate debut during the Panthers' season opening loss to Florida State and had eight carries for 34-yards. The following week, he scored his first career touchdown against New Mexico and finished the win with 12 carries, 119 rushing yards, and a season-high two touchdowns. On December 26, 2013, Conner had a season-high 26 carries for 226-yards and a touchdown during a 30-27 victory over BowlingGreen in the Little Caesar's Bowl. He was named the 2013 Little Caesars Pizza Bowl MVP. He led the team in rushing yards with 799 and rushing touchdowns with eight. Conner's 229 rushing yards broke Tony Dorsett's school record for rushing yards in a bowl game.
He 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. On November 1, 2014, Conner rushed for a career-high 263 rushing yards on a career-high 38 attempts and scored three touchdowns during a 48-51 double-overtime loss to #24 Duke. The next game, he continued to have his second consecutive rushing game over two hundred yards when he had 30 carries for 220-yards and tied his career-high with four touchdowns during a loss to North Carolina. In his sophomore season in 2014, Conner rushed for 1,765 yards on 298 attempts and set an ACC record with 26 rushing touchdowns. He led the ACC in rushing yards and ranked 7th in the FBS. At the end of the season, he was named the ACC Player of the Year and garnered AFCA first-team All-American honors.
On September 5, 2015, Conner tore his Medial collateral ligament during the Panther's season opening 45-37 victory over Youngstown State. He finished the game with eight carries for 77 rushing yards and scored two rushing touchdowns and missed his entire junior season. He was also diagnosed with Hodgkin's Lymphoma during the rehab process and was finally cancer-free during the off-season.
He played in the Panther's season-opener against Villanova and finished the victory with 17 carries for 53-yards and a touchdown while also accounting for three receptions for 15-yards and scored his first career touchdown reception. The next game, Conner had 22 attempts for 117 rushing yards and tied his career-high of four rushing touchdowns in a 39-42 victory over Penn State. He also had four receptions, 29 receiving yards, and a touchdown reception against Penn State. 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. On October 27, 2016, he had 19 carries, a season-high 141 rushing yards and three touchdowns in a 36-39 loss to #25 Virginia Tech.
On December 10, 2016, Conner announced via Twitter that he intends to apply for early eligibility for the 2017 NFL Draft as an underclassman and forgo his senior year at Pitt. Underclassmen have to apply for the draft by January 16, 2017.
When Conner was coming out of college, the majority of scouts and analysts projected him to be picked in the fifth or sixth round. Conner was ranked the 12th best running back available in the draft by Sports Illustrated and the 15th best running back by NFLDraftScout.com. He attended the NFL Scouting Combine, but chose to perform only the 40-yard dash, broad jump, vertical, and bench press. He completed the three-cone drill, short shuttle, and positional drills at Pittsburgh's Pro Day to finish his combine performance.
The Pittsburgh Steelers selected Conner in the third round (105th overall) of the 2017 NFL Draft. Conner was the eighth running back selected in the draft.
On May 11, 2017, the Steelers signed Conner to a four-year contract.
James Conner was raised by his parents, Kelly Patterson and Glen Conner Sr. and is the youngest of five brothers. His brothers are Glen, Richard, Michael and Rico. Glen, Richard and Michael are blood related, while Rico is a stepbrother from his mother's second marriage. He majored in communications at Pitt.
On December 4, 2015, Conner announced he was diagnosed with Hodgkin's Lymphoma. Despite this, he said "I choose to not fear cancer...I will play football again." After tearing his MCL during the Panther's first game of 2015, Conner began attending rehab and began experiencing excessive fatigue and other symptoms, leading doctors to perform a chest X-Ray that revealed Hodgkin's Lymphoma. He had to endure 12 rounds of chemotherapy and had his last chemo appointment on May 9, 2016. During his treatment, Conner continued to participate in non-contact drills with the Panther's football team as much as his body would allow.
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 who Conner saw as an inspirational figure. During Conner's treatment, both players would speak via text but had never met in person.
On May 23, 2016, Conner announced on Twitter that he was cancer free.