In his more than two decades on the professional gridiron, Morrall played for six different teams, starting with his rookie year in 1956 as a first-round selection by the San Francisco 49ers. On September 16, 1957, he was traded along with guard Mike Sandusky to the Pittsburgh Steelers in exchange for linebackerMarv Matuszak and two first-round draft picks. Despite the high cost of the transaction, the Steelers traded him just over a year later to the Detroit Lions in order to obtain future Hall of Famer Bobby Layne. Morrall was with the Lions for the next six years, having his best season in 1963 by throwing for 24 touchdowns and more than 2,600 yards. The following year, he suffered a season-ending shoulder injury in an October 18 contest against the Chicago Bears.
After spending the off-season rehabilitating from his injury, Morrall was dealt by the Lions to the New York Giants for Mike Lucci who had been acquired from the Cleveland Browns, Darrell Dess and a draft pick as part of a three-team transaction on August 30, 1965. Enduring his role during the Giants' rebuilding phase, Morrall threw for 2,446 yards and 22 touchdowns that season, but found himself seeing spot duty over the course of the next two years. He was traded to the Baltimore Colts for an undisclosed draft choice on August 25, 1968. Butch Wilson was sent to the Giants to complete the transaction eight days later on September 2.
When regular Colts signal caller Johnny Unitas was injured in the final exhibition game, Morrall became the team's starter. Morrall proceeded to lead the Colts to a 13-1 record, then added two playoff victories en route to winning the NFL's Most Valuable Player award, leading the Colts into Super Bowl III. However, in one of sport's greatest upsets, the Colts lost 16-7 to the New York Jets, with a second-quarter interception of a pass by Morrall symbolizing the team's luck on the day. Wide receiver Jimmy Orr was wide open near the end zone, but Morrall inexplicably did not see Orr (despite having successfully run the same play earlier in the year). His throw down the middle was short and intercepted by Jim Hudson to blunt the Colts' momentum. Two years later, Morrall again replaced an injured Unitas in Super Bowl V, and the Colts won 16-13 over the Dallas Cowboys on a 32-yard field goal by Jim O'Brien at the end of regulation.
On April 25, 1972, Morrall was claimed on waivers for $100 by the Miami Dolphins, reuniting him with his former Colts head coach, Don Shula. Shula described Morrall as "an intelligent quarterback who's won a lot of ball games for me."
Morrall replaced the injured Bob Griese for the Dolphins during the team's October 15 win over the San Diego Chargers. The victory gave Miami a 5-0 record, with Morrall building on that win to lead the team to the first undefeated regular season in the NFL since 1942 and only undefeated season ever, starting 11 out of 17 games that year. After notching a win in the team's first playoff game against the Cleveland Browns, Morrall struggled against the Pittsburgh Steelers in the AFC Championship game, leading to the return of Griese.
Morrall would remain as a Dolphin quarterback for the next four seasons before finally announcing his retirement on May 2, 1977. Until first Doug Flutie and then Vinny Testaverde almost 30 years later, Morrall was the oldest quarterback to start and win a football game in the NFL. In those 21 seasons, he was part of 255 games, completing 1,379 passes for 20,809 yards and 161 touchdowns.
During a 1989 interview, Morrall was asked what it took to come off the bench and be an effective quarterback and team leader. His response was, "When you get the chance to do the job, you have to do the job. That's all there is to it."