Duffey was redshirted his first year at Texas Tech and did not play.
2017
Duffey was suspended from the team and university for spring and summer terms. Chris Cook, a spokesperson for Texas Tech, stated the suspension was imposed by the university and not the team. It was later revealed in April that Duffey was found responsible for two counts of sexual misconduct, violating Title IX policies. A grand jury found that there was not sufficient cause for a criminal prosecution. Duffey's suspension ended in August and he returned to the university and team. Duffey only played one game in 2017, appearing late in the season opener against Eastern Washington. Duffey finished 2/2 for 16 yards along with 4 rushing attempts for 6 yards in the 56–10 victory.
2018
Duffey entered the 2018 season in a competition for the starting quarterback position against junior McClane Carter and freshman Alan Bowman. Carter would start in the season opener against Ole Miss but suffered a high ankle sprain in the 2nd quarter and was replaced by Bowman. Duffey played his first game of the season next week at home against Lamar in relief of Bowman, with Texas Tech up 42–0. He would finish 7/9 for 93 yards and an interception and led the team in rushing with 81 yards and a touchdown. On September 29 against West Virginia, Bowman suffered a partially collapsed lung late in the 2nd quarter with Duffey replacing him. The Red Raiders trailed 35–10 when Duffey entered the game and he led a comeback attempt, but threw a costly pick six in the 4th quarter with Texas Tech losing 34–42. Duffey would start the next game, against TCU, with Bowman still out due to injury. He would finish 13/24, for 190 yards, a touchdown, and an interception along with 83 yards rushing and a rushing touchdown in the 17–14 victory. Duffey's next start would be on November 10 against Texas. Duffey finished 37/47 for a career high 444 yards with 4 touchdowns, but also threw an interception and fumbled the ball twice in the 34–41 loss. Duffey would struggle the following week against Kansas State, finishing 19/27 for 150 yards with an interception. Duffey would finish the 2018 season as the team's leading rusher, rushing for 369 yards with 4 touchdowns.
2019
Duffey would enter the 2019 season as the third quarterback on Texas Tech's depth chart behind returning starter Alan Bowman and Rice transfer Jackson Tyner. Bowman suffered a left shoulder injury against Arizona with Tyner being named the Red Raiders' starting quarterback for the Oklahoma game. Tyner would be replaced by Duffey late in the first quarter after Tyner struggled. Duffey finished 11/20 for 120 yards in the 16–55 loss. Following the game, head coach Matt Wells announced that Duffey would be the team's starting quarterback. The following week, Duffey would lead the Red Raiders in a 45–35 upset victory over the no. 21 Oklahoma State Cowboys. Duffey had his second career 400-yard passing game, finishing 26/44 for 426 yards with 4 touchdowns, rushed for another touchdown and committed no turnovers. For his performance, Duffey received several weekly awards, including the Big 12 Offensive Player of the Week, the Maxwell Award Player of the Week, and the Davey O'Brien Quarterback of the Week. On December 13, Duffey had entered the NCAA's transfer portal.
2020
On January 8, it was announced that Duffey would be transferring to Tulane. On January 10 he announced on Twitter he would open again his transfer and not go to Tulane.
