Rypien spent his first two years as a professional on the Redskins' injured reserved list, first with a bad knee in 1986, then a bad back in 1987. He watched from the sidelines as the Redskins won Super Bowl XXII under coach Joe Gibbs in January 1988 behind the quarterbacking of veteran Doug Williams.
Rypien became the second stringer after Jay Schroeder, who had lost his job to Williams late in the 1987 season, was traded to the Los Angeles Raiders. In Week 4 against the newly relocated Phoenix Cardinals, Rypien got his first chance to start for an injured Williams and threw for 303 yards and two touchdowns in a 30-21 loss. In six starts, Rypien went 3-3 and he appeared in nine games overall, including a four-touchdown game in a rematch against the Cardinals. He threw for 1,730 yards in those games and finished with three more touchdowns than Williams had, by a count of 18 to 15.
Named the starter for 1989 ahead of the injured and aging Williams, Rypien emerged as a star quarterback as he threw for 3,768 yards with 22 touchdowns and led the Redskins to a 10-6 record. The team missed the playoffs but Rypien received a bid as an injury replacement for Joe Montana and Don Majkowski in that year's Pro Bowl (NFC coach John Robinson elected to bring only one injury replacement for his intended starter and #2 quarterback).
Rypien was best known for his phenomenal accuracy as a deep passer,developing an incredible sense of timing with receivers downfield. A running joke among sportswriters in Washington was that Rypien could only throw "ducks" in a ten yard game of catch going during warmups, but threw such a beautiful, accurate deep ball that from sixty yards away, he could play catch with someone sitting down. According to former head coach Joe Gibbs, "Rypien's sideline throws would wobble and didn't look all that pretty. But that man could seriously throw the deep stuff." A 1992 Sport Magazine article touted him as one of the best deep passers ever.
1991 was Rypien's best season; he threw for 3,564 yards and 28 touchdowns with 11 interceptions, leading the Redskins to Super Bowl XXVI after recording a 14-2 regular season record. He was named the MVP (Most Valuable Player) of the game, passing for 292 yards and 2 touchdowns and leading his team to a 37-24 win over the Buffalo Bills. Rypien, a native of Calgary, Alberta, became the first foreign-born player to earn the honor. Rypien was named to the Pro Bowl in both 1989 and 1991.
Rypien was one of several players to benefit from the team's success following their championship season. The Redskins signed him to a 3-year, $9 million deal entering the 1992 season. However, the team battled age and injuries and finished the regular season with a 9–7 record, barely making the playoffs. His passing yardage was a respectable 3,282 yards, but his passer rating fell from 97.9 in 1991 to 71.7 in 1992 and his interceptions outnumbered his touchdowns 17 to 13. Although a dominant team performance in the playoffs brought victory over the Minnesota Vikings in an NFC Wild Card away game, the Redskins eventually lost on a rainy, muddy field in a bruising game vs. the San Francisco 49ers, and the Rypien era was essentially over. Under new Head Coach Richie Petitbon, Rypien had his best training camp in 1993 and expectations were high following a Monday Night win over the defending Super Bowl Champion Dallas Cowboys. However, Rypien injured his knee in Week 2 against the Arizona Cardinals and the team began a precipitous slide toward a 4–12 season finish.
When he was healthy enough to return, Rypien performed spot duty, sharing time with the newly acquired Rich Gannon. The Redskins hired Norv Turner as their head coach in 1994. Rypien participated in offseason workouts, but the team released him from his contract. He went on to become a backup, serving with the Cleveland Browns in 1994, the St. Louis Rams in 1995 and 1997, and the Philadelphia Eagles in 1996. He signed with the Atlanta Falcons for the 1998 season but never made it to Atlanta. His son's death from a malignant brain tumor that August caused Rypien to leave the game (although he would return in 2001 for a stint with the Colts). He would return to football with the Indianapolis Colts in 2001. His last touchdown pass came in relief of Eagles quarterback Ty Detmer, an 8-yarder to Irving Fryar with five seconds remaining in a 37-10 loss to the Colts. In August 2002, Rypien was signed by the Seattle Seahawks as a backup quarterback, played in two preseason games and finished 13-of-21 passing for 97 yards, but was cut early in September. His last professional game was on June 10, 2006; as part of a promotional gig, Rypien played one game for the Rochester Raiders of the Great Lakes Indoor Football League.
In 11 NFL seasons, Rypien completed 1,466 of 2,613 passes for 18,473 yards and 115 touchdowns, with 88 interceptions. He rushed 127 times for 166 yards and 8 touchdowns.
An avid golfer, Rypien has been known to participate in charity tournaments at various locations across the nation. He has played in one PGA Tour event (1992 Kemper Open) and one Nationwide Tour event ('00 BUY.COM Tri-Cities Open) and in both instances missed the cut by a substantial margin. He has been a regular competitor at the American Century Championship, the annual competition to determine the best golfers among American sports and entertainment celebrities. What is most notable about Rypien's golfing exploits is that he won the inaugural event in 1990, and won his second crown in 2014, a full 25 years apart. He has a total of eleven top ten finishes. The tournament, televised by NBC in July, is played at the Edgewood Tahoe Golf Course in Lake Tahoe, Nevada.
^Patrick Seitz (2011-07-30). "Lingerie Football League needs stars". Tech-media-tainment. Retrieved 2012-04-22. For season three, the LFL has two stars in the making: Seattle Mist quarterback Angela Rypien, the daughter of Super Bowl MVP quarterback Mark Rypien, and Toronto Triumph linebacker Krista Ford, niece of Toronto Mayor Rob Ford and daughter of City Councillor Doug Ford. They’re relatives of sports and political figures, so that gives news writers a hook to cover the games. So far, the LFL has gotten scant coverage from the mainstream media, which treats it like a peep show. Adding stars can only help the fledgling league.