Saberhagen was drafted out of high school by the Kansas City Royals in the 19th round of the 1982 Major League Baseball Draft and made his major league debut on April 4, 1984. He made an immediate impact with the team, compiling a 10–11 record and a 3.48 ERA. The Royals made the postseason but lost to the Detroit Tigers. Saberhagen pitched well in his first postseason start, giving up two runs in 8 innings.

In 1985, the 21-year-old Saberhagen established himself as the ace of the staff, going 20–6 with a 2.87 ERA, leading the Royals to a World Series championship (and being named MVP of the Series along the way, pitching two complete games in the Series, including a shutout in Game 7), and winning the American League Cy Young Award. In 1987, Saberhagen had an excellent year, going 18–10 with a 3.36 ERA. 

In 1989, he compiled a record of 23–6 with a 2.16 ERA, leading both leagues with 12 complete games, and finishing third in strikeouts. Before his July 26, 1989 start against the Boston Red Sox, Saberhagen had a record of 9–5. Over the next two months, he compiled a record of 14–1 with four shutouts. He also led the league in innings pitched, complete games, and strikeout to walk ratio. For his efforts, Saberhagen won his second Cy Young Award as the American League's best pitcher.

In 1991, Saberhagen went 13–8 with a 3.07 ERA. On August 26 of that year, he no-hit the Chicago White Sox 7-0 at Royals Stadium. On December 11, 1991, he was traded to the New York Mets. He posted several solid seasons, winning 14 games for the New York Mets in the strike shortened 1994 season and won 15 games for the Boston Red Sox in 1998.  Saberhagen didn't pitch at all in 1996 due to injury but attempted a comeback with the Boston Red Sox and went 15-8 and 10-6 in 1998 and 1999. He won also the Sporting News Comeback Player of the Year in 1998. After missing the entire 2000 season, Saberhagen made a comeback in 2001 but pitched in only three games. He retired at the end of the season.

In 2005, he was inducted into the Kansas City Royals Hall of Fame.  He became the head baseball coach for the Calabasas Varsity baseball team in 2008.