McGwire was born in Pomona, California, and is a former Parade Magazine All-American at Claremont High School in Claremont, California. He made Street & Smith's top 50 list, was named honorable mention all-America by USA Today, completed 203 of 328 passes (61.9 percent) for 3,172 yards and 33 touchdowns as a senior, punted for a 40-yard average, led his team to California's East Sectional title (includes 550 teams), was named California's 1985 Offensive Player of the Year, made the Cal-Hi Sports first team all-state squad, quarterbacked squad to three-year record of 36–3–1 including 13–1 mark as a senior, passed for 345 and 303 yards in sectional championship games as junior and senior, was named 1985 state MVP, and accumulated three-year varsity totals of 6,559 yards passing and 65 touchdowns. He was also a double-figure scorer and rebounder his last two seasons in basketball.
McGwire initially enrolled with the University of Iowa where he played for two seasons in limited action before transferring to San Diego State University. In 1989, McGwire passed for 3,651 yards and in 1990 threw for 3,883 yards and 27 touchdowns and was named First-Team All-Conference and earned the title of Offensive Team Captain and won team MVP honors as a Senior.
McGwire was a first-round draft pick (16th overall) to the Seattle Seahawks in 1991 and went on to play for five seasons in the National Football League (NFL), from 1991 to 1995. He played four seasons for the Seahawks and one season for the Miami Dolphins. He was a backup to Dave Krieg in his rookie season but was expected to be the quarterback of the future. In his second season, he was underwhelming in the pre-season and was named third-string quarterback behind Stan Gelbaugh and Kelly Stouffer. In 1993, the Seahawks drafted Rick Mirer out of the University of Notre Dame in the first round, seemingly giving up on McGwire. In 1994 after an injury to Mirer, McGwire got the first and only extended playing time of his career. He started three games, in which the team went 1–2, and on the season threw 105 passes, completing 51 of them for 578 yards and one touchdown. The brief playing time did not materialize into anything larger however, and that would be his last season for the Seahawks. After spending one season in Miami he was out of football.
McGwire is generally considered a "first round bust," given the fact that he was the first quarterback taken in the 1991 draft that saw Brett Favre go in the second round.
At six feet, eight inches, McGwire is the tallest quarterback in NFL history. McGwire's brother is former Major League Baseball player Mark McGwire. Dan McGwire is currently the president of an enhanced water company in Reno, Nevada. McGwire has three daughters, Morgan, Mallory and Gracen. Morgan, 6-foot-3, played four years of basketball at Santa Clara and scored over 1,000 points in her career. Mallory, a 6-foot-5 post, plays basketball at the University of Oregon.