Majkowski was drafted by the Green Bay Packers in the 10th round in 1987. He was originally issued jersey #5, but switched to #7 the following season in anticipation that #5 would be retired for Paul Hornung. The jersey was never officially retired, but Majkowski is still the last Packer to have worn #5. As a rookie, Majkowski split time with Randy Wright whom he also shared quarterback duties with during the 1988 season.
Nicknamed The Majik Man, Majkowski broke out during the 1989 Green Bay Packers season. He was given the starting job and Randy Wright was released. Majkowski had one of the finest seasons in Packers history. He completed 353 passes in 599 attempts. His 4,318 passing yards led the NFL. He also threw for 27 touchdowns. Notably, the Packers won their first game against the hated rival Chicago Bears since 1984. The key was a touchdown play first nullified by an illegal forward pass by Majkowski; then upheld by instant replay as a legal pass; it is known in history as the "Instant Replay Game". The season ended with 10 wins and 6 losses; Majkowski capped the season with his being selected to the Pro Bowl.
Majkowski's success was cut short when, in the 10th game of the Packers' 1990 season, Majkowski was injured when he was upended and tackled on his shoulder by Freddie Joe Nunn. Nunn drew a personal foul on the play. At first thought to be a bruise, Majkowski's injury turned out to be more serious, a torn rotator cuff. The Packers finished the season using backups Anthony Dilweg and Blair Kiel.
During the course of the 1991 season, Majkowski was benched and replaced by Mike Tomczak as starter, but resumed starting duties at the beginning of the 1992 season. On a play on September 20, 1992 against the Cincinnati Bengals, Majkowski tore a ligament in his ankle. He was replaced after the play by Brett Favre, who completed the game. Favre went on to start in every consecutive Packers game through the 2007 season.
Majkowski finished his career for the 1995 and 1996 Detroit Lions also in a backup role. In his final season, Majkowski faced Brett Favre and the Green Bay Packers in November completing 15 of 32 passes for 153 yards and a TD. He was also sacked 5 times. His final game ever played was in Detroit versus the Seattle Seahawks. He completed 18 of 23 passes (78% completion percentage) for 157 yards and 1 TD. His quarterback rating was 91.5.