Career highlights during his 1988-1991 run as Pittsburgh's starting QB included ranking 4th in the NFL in average yards per pass completion in 1988 and ranking 10th in the league in passer rating in 1990. Brister had five scoring passes that were 65 yards or longer in 1988, including an 89-yard touchdown to Louis Lipps vs the Philadelphia Eagles on November 13 that was the longest pass completion by a Steeler in Three Rivers Stadium history. In 1989 he set a team record with 15 consecutive pass completions in a road win over Detroit, including a 48 yarder to Lipps. Brister also set a team record in 1989 throwing 178 consecutive passes without an interception. It was 1990 that Brister established career highs for starts (16), yards passing (2,725) and touchdown passes (20). Brister missed 8 games with injuries in 1991, setting up a competition with back up Neil O'Donnell for the starting job. Pittsburgh went 5-3 when Brister played, only 2-6 with O'Donnell as a starter. Brister was the starting quarterback during Hall Of Fame Coach Chuck Noll's final post season run with the Steelers, winning the 1989 AFC Wild Card in overtime on the road against the Houston Oilers, then losing a close game to eventual AFC champion Denver Broncos. Brister led an 82-yard drive at the end of the 4th quarter to tie the Houston game and force overtime. Against Denver, he passed for 229 yards and 1 touchdown, with no turnovers.
After brief stops as a backup quarterback for the Eagles and New York Jets, Brister sat out the 1996 season. In his first season in Philadelphia in 1993, Brister ranked 7th in the league in passer rating and 4th in lowest interception percentage, starting 8 games with two relief appearances subbing for an injured Randall Cunningham. Brister's interception percentage that year was the lowest in Eagles team history for more than a decade until eclipsed by Donovan McNabb. Before the 1998 season, Jeff Lewis had fallen out of favor with the Broncos; thus, Brister became the primary backup QB. During the 1998 season, Elway was forced to sit out a number of games due to injury and Brister started those games in his place. He played well and the Broncos went undefeated in all of his starts (4-0); Brister also broke the team's (then) record for longest rushing touchdown by a quarterback[4] and recorded a higher passer rating than Elway. However, when Elway retired in 1999, Brister was passed over for the starting spot in favor of Brian Griese, and the Broncos released him after that season. During his three seasons with the Broncos, he won two Super Bowl rings.