Guidry won the AL Cy Young Award in 1978 as the best pitcher in the AL. He also won five Gold Glove Awards, given for superior fielding, and appeared in four All-Star games. Guidry served as captain of the Yankees from 1986 through 1988, and his number has been retired by the Yankees.
In 1978, Guidry posted a career year, one of the best in the modern era. Against the California Angels on June 17, he struck out a Yankee-record 18 batters. Guidry's 18-strikeout performance is usually cited as the launching pad of the Yankee Stadium tradition of fans standing and clapping for a strikeout with two strikes on the opposing batter.
For the season, Guidry went 25-3, in a season that is among the top 10 for winning percentage in baseball history. He led the league with a sparkling 1.74 ERA, 25 wins, a .893 winning percentage, 9 shutouts, 248 strikeouts, and 6.15 hits allowed per 9 innings pitched. He held batters to a .193 batting average, .249 on base percentage, and .279 slugging percentage. He was particularly effective with 2 outs and runners in scoring position (.152/.221/.253), and in the 9th inning of games (.119/.200/.136). Guidry's success during 1978 was due in large part to mastering the slider. He began throwing the pitch the year before, and was able to use the sharp-breaking slider to complement his great fastball throughout the season.
Guidry's 25th win of the regular season was his most significant, as he was the winning pitcher in the Yankees' 5-4 win over the Boston Red Sox in a one-game playoff at Fenway Park in Boston to decide the American League East division winner. The game is best known for Bucky Dent's seventh-inning, three-run home run off Mike Torrez (who, as a Yankee pitching mate of Guidry's just the year before, had recorded the final putout of the 1977 World Series) that gave the Yankees a 3-2 lead. In the second inning of that game, Guidry himself had given up a home run to Carl Yastrzemski—the only home run a left-hander would hit against him all season.
Over the next seven seasons, Guidry amassed a 113-57 win-loss record. Guidry also won the Gold Glove Award five straight times (1982–86). However, arm problems that began in 1981 finally began dramatically affecting his performance. He retired from baseball on July 12, 1989, after shoulder surgery did not improve his performance.
As well as winning the 1978 Cy Young Award, Guidry was named The Sporting News AL Pitcher and Major League Player of the Year. Guidry was named "Lefthanded Pitcher" on The Sporting News AL All-Star Teams in 1978, 1981, 1983 and 1985. Guidry also finished in the top 10 in the American League Cy Young voting six times (1977–79, 1981, 1983 and 1985) over a nine-year span.
On August 7, 1984, Guidry struck out three batters (Carlton Fisk, Tom Paciorek and Greg Luzinski) on nine pitches in the ninth inning of a 7-0 win over the Chicago White Sox. Guidry became the eighth American League pitcher and the 20th pitcher in Major League history to accomplish the so-called "immaculate inning." He was the first pitcher to do so in the 9th inning of a complete game, a feat which has since been matched only once.
Guidry served as co-captain of the Yankees along with Willie Randolph from March 4, 1986 until July 12, 1989.
Guidry was also noted for having a very good pickoff move.
Guidry joined Yankee's Manager Joe Torre's coaching staff as pitching coach in the 2006 season, replacing Mel Stottlemyre. Under Guidry's tenure, the Yankees' pitching staff enjoyed mixed results. The pitching staff's ERA decreased from 4.52 in 2005 to 4.41 in 2006 under his first year of coaching, though in 2007, the team ERA increased to 4.49 (or 17th overall in the Major leagues).
However, Guidry was criticized in 2007, because the highly-acclaimed pitching staff was underachieving. The Yankees pitching staff in 2007 walked the sixth most batters overall in the Major Leagues; this was the most walks in a season for a Yankees pitching staff since the 2000 season. Torre's departure from the Yankees following the 2007 season ended Guidry's tenure as pitching coach. Though he was interested in returning to the Yankees for the 2008 season, he was not offered a position on new manager Joe Girardi's coaching staff. He did return to the Yankees as a spring training instructor.
Former New York Times writer Harvey Araton wrote a book called "Driving Mr. Yogi: Yogi Berra, Ron Guidry, and Baseball's Greatest Gift" that profiles the friendship Guidry has with Yankees' Hall of Fame catcher (and Guidry's former coach and manager) Yogi Berra. During Spring Training, Guidry is assigned to drive Berra around.