A righthander, Sutcliffe was a three-time All-Star. He won the National League Rookie of the Year award in 1979 and the National League Cy Young Award in 1984.

Sutcliffe broke into the majors to stay in 1979. Considered a long shot to make the team in spring training, he went on to win 17 games for the Los Angeles Dodgers and was the first of four consecutive Rookies of the Year for the Dodgers from 1979-1982 (Steve Howe, Fernando Valenzuela, and Steve Sax were the others). Sutcliffe and Dodgers manager Tommy Lasorda got along poorly, and after Lasorda left Sutcliffe off the Dodgers' 1981 postseason roster, Sutcliffe burst into Lasorda's office, overturned his desk and smashed chairs. Lasorda promptly traded Sutcliffe to the Cleveland Indians for Jorge Orta, a journeyman outfielder.

Sutcliffe won 31 games over the course of the next two seasons for Cleveland and led the American League in earned run average in 1982. In mid-1984, Cleveland traded a struggling Sutcliffe to the Chicago Cubs for Mel Hall and Joe Carter. Sutcliffe rebounded and won 16 games for the Cubs while losing only one, helping them to the division championship (their first championship of any kind since 1945) and won the Cy Young Award. He also finished fourth in the league MVP voting. When he re-signed with the Cubs as a free agent the following year, his contract briefly made him the highest-paid pitcher in baseball.

A hamstring pull in 1985 followed by a series of arm injuries limited Sutcliffe's effectiveness over the next two seasons. In 1987, he bounced back to win 18 games and finished second in the league's Cy Young voting.

In 1989, Sutcliffe won 16 games and made his final All-Star appearance--Lasorda was the manager. He also helped the Cubs to another division title, but the Cubs lost to the San Francisco Giants in the playoffs.

Recurring arm injuries caused Sutcliffe to miss most of the 1990 and 1991 seasons and the Cubs did not offer him a contract for the next season. Signing with the Baltimore Orioles, Sutcliffe went 16-15 and 10-10 in 1992 and 1993, starting the first game at Oriole Park at Camden Yards. He wound up his career with the St. Louis Cardinals in 1994, going 6-4 in an injury-plagued season. He retired with a career record of 171-139, with an ERA of 4.08.

After his retirement from baseball, Sutcliffe became a color commentator for ESPN and a minor-league pitching coach in the San Diego Padres system.

On May 10, 2006 after a long day of drinking and golfing with comedian Bill Murray, Sutcliffe attended a night game between the San Diego Padres and Milwaukee Brewers in San Diego. He was invited to the booth with Channel 4 broadcasters Mark Grant and Matt Vasgersian where he gave a rambling and incoherent interview mentioning off-the-wall subjects such as George Clooney, his daughter's "mission", and after he asked Matt Vasgersian what he was still doing in San Diego his microphone was cut off. This obviously was an error on the part of the producer of the broadcast as Sutcliffe was obviously drunk. As a result, ESPN suspended Sutcliffe for one game.