He played college football for the Oklahoma State Cowboys, where he was a three-year starter and won the Johnny Unitas Golden Arm Award during his last year.

During his senior season, he accounted for 80 total touchdowns and threw for 4,400 yards as he led the Trojans to a 15–0 record, 4A State Championship and #7 national ranking.

He played in the Annual Shrine Bowl All-Star game and was named the offensive MVP as he led South Carolina on a game-winning drive in the final 20 seconds.

[13] Rudolph is the winner of the 2017 Johnny Unitas Golden Arm Award, given annually to the country's outstanding senior college quarterback.

He met with scouts and team representatives from the Pittsburgh Steelers, New York Giants, and Los Angeles Chargers privately after completing his pro day.

[15] He attended private workout and visits with the New England Patriots, Buffalo Bills, New Orleans Saints, Cincinnati Bengals, Steelers, New York Giants, and Chargers.

[16] At the conclusion of the pre-draft process, Rudolph was projected to be a second round pick by the majority of NFL draft experts and scouts.

[25] Throughout training camp, Rudolph competed against Landry Jones and Joshua Dobbs for the backup spot behind Ben Roethlisberger.

[28] During Week 2 against the Seattle Seahawks, Rudolph relieved an injured Roethlisberger in the second half and threw for 112 yards, two touchdowns, and an interception as the Steelers narrowly lost 28–26.

[29] Following the announcement that Roethlisberger would miss the rest of the season due to season-ending elbow surgery, Rudolph became the Steelers' starting quarterback.

[44] In the following week against the still-winless Bengals, Rudolph struggled again, throwing for 85 yards and an interception before being benched for Hodges in the third quarter who led the Steelers to a 16–10 comeback victory.

[45][46] Two days later, head coach Mike Tomlin announced that Hodges would remain the starting quarterback for the following week's game against the Browns.

[50] Rudolph was named second string quarterback on the depth chart going into the 2020 season behind Ben Roethlisberger, beating out Joshua Dobbs for the backup role.

[51] During Week 9 against the Dallas Cowboys, Rudolph came into the game in the second quarter after Ben Roethlisberger went to the locker room with an ankle injury.

[53] Rudolph also made appearances in relief of Roethlisberger in the 4th quarter of blowout wins against the Cleveland Browns, Cincinnati Bengals, and Jacksonville Jaguars.

[54][55] On December 29, 2020, with the Steelers already locking up the AFC North with a record of 12–3, head coach Mike Tomlin announced that Rudolph would start the season finale against the Browns in order to rest Roethlisberger in preparation for the playoffs.

[63] On September 5, 2022, the official Steelers depth chart was released showing Rudolph being listed at second-string quarterback behind Mitchell Trubisky and ahead of rookie Kenny Pickett.

The following day, Rudolph was demoted to third-string quarterback with head coach Mike Tomlin citing a "clerical error" in the original depth chart.

Following an injury to Kenny Pickett and poor play by Trubisky, Rudolph was named the starter for the Steelers' Week 16 game against the Cincinnati Bengals.

[82] He started against the Buffalo Bills in the Wild Card round, completing 22 of 39 passes for 229 yards with two touchdowns and one interception in the Steelers' 31–17 loss.

He replaced an injured Will Levis in the first half and led the Titans on seven scoring drives, securing their first win of the season with a 31–12 victory.

[89] He started the next two games against the Indianapolis Colts and the Jacksonville Jaguars, both ending in a loss, before alternating with Levis in the season closer against the Houston Texans.