He played college football for the North Carolina Tar Heels and was selected second overall by the Chicago Bears in the 2017 NFL draft.

Due to inconsistent play, he was not re-signed by the Bears after his rookie contract expired in 2021 and spent one season as a backup with the Buffalo Bills.

Trubisky committed to the University of North Carolina at Chapel Hill to play college football under head coach Larry Fedora.

In the 2014 Quick Lane Bowl, he was 7-of-9 for 65 yards and a touchdown, which was a pass to receiver Kendrick Singleton, in the 40–21 loss to the Scarlet Knights.

[16] In the 2016 Sun Bowl against the Stanford Cardinal, he was 23-of-39 for 280 yards, two touchdowns, and two interceptions in his final collegiate game, a 25–23 loss.

Trubisky decided to forgo his senior season and declared for the 2017 NFL draft on January 9, 2017, opting to give up his final year of college eligibility.

[33][34] After the Bears started the season with a 1–3 record, head coach John Fox benched Glennon and Trubisky was named the starter for Week 5.

[35][36][37] Trubisky made his first regular season start on October 9, 2017, against the Minnesota Vikings, where he completed 12-of-25 passes for 128 yards, a touchdown, and an interception, as the Bears lost 20–17 on Monday Night Football.

[42] The following week, Trubisky completed 12-of-15 passes for 102 yards and a touchdown against the 49ers, but a late field goal by Robbie Gould lifted the 49ers to a 15–14 victory.

[43] During Week 14, however, he completed 25-of-32 passes for 271 yards and a touchdown to seal a 33–7 blowout win over the Cincinnati Bengals, snapping a five-game losing streak as well as posting a 112.4 passer rating.

[44] In Week 15, he struggled against the Detroit Lions; despite finishing with 314 passing yards and a touchdown, he also threw three interceptions as the Bears lost 20–10.

[46] Fox was fired after the 2017 season and was replaced by Kansas City Chiefs offensive coordinator Matt Nagy, who expressed an interest in working with Trubisky after the two met prior to the 2017 draft.

[52] Success came in week 4 against the Tampa Bay Buccaneers: he completed 19-of-26 passes for 354 yards, threw for six touchdowns (five in the first half), and got a passer rating of 154.7.

[58] The following week, he hit Tarik Cohen for a 70-yard touchdown in the first quarter, ending the day with 220 yards in the win over the New York Jets.

Despite his struggles, the Bears defense made four interceptions off Rams quarterback Jared Goff and won by a score of 15–6.

[75] However, Cody Parkey's potential 43-yard game-winning field goal failed – off the post and then crossbar – and resulted in a Chicago defeat.

Trubisky ended his playoff debut having completed 26 of 43 passes for 303 yards, one touchdown, and a passer rating of 89.6; the yards and completions set franchise postseason records, while Trubisky became the youngest Bears quarterback to throw a touchdown pass in the playoffs since Doug Flutie in 1986.

[79] The following week against the Denver Broncos, Trubisky threw 16 times for 120 yards, including a 25-yard completion on fourth down to wide receiver Allen Robinson with only eight seconds in the game that set up a 53-yard game-winning field goal by kicker Eddy Piñeiro.

He suffered a hip pointer while being sacked by Michael Brockers and was benched late in the fourth quarter for Daniel in the 17–7 loss.

[95] The following week against Dallas Cowboys, Trubisky rebounded from throwing an opening-drive interception at the Cowboys' one-yard line by recording 244 passing yards, three touchdown passes, and 63 rushing yards, including a 23-yard rushing touchdown on a read option play as the Bears won 31–24.

[103] In the season opener against the Lions, Trubisky started off slow as he completed eight passes on 20 attempts for 110 yards in the first half, while the Bears trailed 23–6 entering the fourth quarter.

[104] During the final period, he saw marked improvement with eight of ten passes completed for 89 yards and three touchdowns, scoring 21 unanswered points as the Bears came back for the 27–23 victory.

"[105] The following week against the New York Giants, Trubisky completed 13 of 18 passes for 159 yards and a pair of touchdowns in the first half as the Bears pulled ahead 17–0.

[108] Trubisky briefly saw action in Week 8 against the Saints as a Wildcat formation quarterback, recording a three-yard run on a drive that ended with a field goal.

The idea to integrate Trubisky for such plays began development shortly after his benching, with Nagy explaining in his post-game conference that it was "a weapon for us to be able to use his legs, then obviously be able to throw the ball, as well.

[110] On November 27, the Bears announced Trubisky as the starter for their Week 12 game against the Packers on Sunday Night Football due to Foles dealing with a hip injury.

[119] During the Wild Card Round of the 2020–21 NFL playoffs, Trubisky completed 19 of 29 passes for 199 yards and one touchdown as the Saints defeated the Bears 21–9.

[131] On September 6, 2022, Trubisky was named the Steelers' starting quarterback over Kenny Pickett for their Week 1 game against the Bengals.

[133] After throwing for 168 yards with a touchdown and an interception in the Week 2 loss at home against the Patriots, there were chants of "We want Kenny" heard among the Pittsburgh crowd.

With Pickett out, Trubisky was the starter in Weeks 14 and 15, completing 38 of 58 pass attempts for 359 yards, two touchdowns, and three interceptions as Pittsburgh lost both of his starts.