Heinrich played quarterback at Washington in Seattle, leading the nation in passing in 1950 and 1952, and setting many of the school's passing records. His 60.9 completion percentage in 1950 set an NCAA record. Heinrich missed the 1951 season due to a pre-season shoulder separation, and was selected in the third round of the 1952 NFL Draft, but stayed in college and played his fifth-year senior season with the Huskies in 1952. He was inducted into the U.S. Army that November, prior to the Apple Cup in Spokane against Washington State, but was granted a pass to play. The Cougars had won the previous year in Husky Stadium while Heinrich was sidelined, but he led the Huskies to a 33–27 victory in 1952, and finished 3–0 in his career against WSC. Heinrich played two seasons with hall of fame running back Hugh McElhenny. They were expected to play together for three, but Heinrich's shoulder injury put junior Sam Mitchell and sophomore Dean Rockey at quarterback in 1951; after three wins in their first four games, Washington went winless and fell to 3–6–1.
Heinrich was selected by the New York Giants in the third round of the 1952 NFL Draft with a future draft pick, which allowed the team to draft him before his college eligibility was over. He served in the military for just under two years, and also got a chance to play football for Fort Ord. He missed the 1953 season and reported to the Giants in 1954. While in the army, he played for the Fort Ord Warriors, which included running back Ollie Matson. In his six seasons with the Giants, he saw action in three NFL championship games, while being the starting quarterback of the 1956 title team. With Vince Lombardi as the Giants' offensive coordinator, Heinrich split time at quarterback with Charlie Conerly, with him being used to probe defenses and Conerly coming into the games to capitalize on weaknesses.
He returned as a player in 1962 after the American Football League Oakland Raiders bought his rights from the NFL's Cowboys. The Raiders needed quarterback depth after learning that the previous year's No. 1 draft choice, Tom Flores, would miss the season due to a lung infection.
In 1976, Heinrich began his broadcasting career, working first on Washington Huskies games and also as the first radio game analyst for the Seattle SeahawksRadio Network and then becoming an analyst for the 49ers' games. In 1983 and 1984, Heinrich was a color analyst for ESPN and ABC broadcasts of the United States Football League. Heinrich worked with Preview Sports Publications, with whom he published the magazines Don Heinrich's College Football and Don Heinrich's Pro Preview, until his death. In 1991, he was the analyst for Pac-10 games on Prime Ticket, a cable channel based in Los Angeles.
