During his senior year in November 1963, Hunter's right foot was wounded by a brother in a hunting accident; he lost one of his toes and shotgun pellets lodged in his foot. The accident left Hunter somewhat hobbled and jeopardized his prospects in the eyes of many professional scouts, but the Kansas City Athletics signed Hunter to a contract. Hunter was sent to the Mayo Clinic that year so that surgeons could work on his foot. He recovered in LaPorte, Indiana at the farm of Athletics owner Charles O. Finley.
Finley gave Hunter the nickname "Catfish" in 1965 because he thought his 19-year old pitcher needed a flashy nickname. A story circulated that Hunter's family gave him the nickname as a child when he went missing and was later found with a string of catfish; there seems to be no truth to that explanation. Hunter never played in the minor leagues and his first major league victory came on July 27, 1965 in Fenway Park against the Boston Red Sox. In 1966 and 1967, Hunter was named to the American LeagueAll-Star team.
Prior to the 1968 season, Finley moved the A's from Kansas City to Oakland. On Wednesday, May 8, against the Minnesota Twins, Hunter pitched the ninth perfect game in baseball history. He became the American League's first perfect game pitcher since Charlie Robertson in 1922 (excluding Don Larsen's perfect game in the 1956 World Series), as well as the franchise's first no-hit pitcher since Bill McCahan in 1947 with what were then the Philadelphia Athletics. The game was scoreless until the bottom of the seventh inning; at the plate, Hunter got three hits and drove in three of Oakland's four runs with a squeeze bunt in the seventh and a bases-loaded single in the eighth.
Hunter continued to win games, and in 1974 received both The Sporting News's "Pitcher of the Year" award and the American League Cy Young Award after going 25–12 with a league leading 2.49 earned run average. The A's also won their third consecutive World Series. After a contract violation on an annuity by Finley in 1974, Hunter won arbitration in December and he was allowed to leave the Athletics as a free agent. Hunter's statistics while he was with the Athletics were impressive: four consecutive years with at least 20 wins, and four World Series wins without a loss. He had won 161 games for the A's, 131 in seven seasons in Oakland and 30 in his first three seasons in Kansas City. Hunter recalled being scared after he was declared a free agent. "We don't belong to anybody," he told his wife.
Finley attempted to have the arbitration ruling overturned, but was unsuccessful after several appeals. Further details of Finley's history with Hunter gave the A's owner added negative publicity. Hunter became known as baseball's "first big-money free agent".
Hunter got off to a rough start going 0–3 in his first three starts, but settled down and was named to his seventh All-Star team. He led the league in wins (23) for the second year in a row, and also led the league in innings pitched (328) and complete games (30) to finish second to Jim Palmer of the Baltimore Orioles in the American League Cy Young balloting. Hunter also became only the fourth (and last) American League pitcher to win 20 games in a season for five consecutive seasons (1971–1975). The others were Walter Johnson (10), Lefty Grove (7), and Bob Feller (5). Palmer had two four-year streaks (1970–1973 & 1975–1978) for eight in nine years.
In 1976, Hunter won 17 games, led the Yankees in complete games and innings pitched, and was again named to the All-Star team. The Yankees won three straight pennants with Hunter from 1976 to 1978. However, arm injuries plagued Hunter beginning in 1978. In spring training, he was diagnosed with diabetes and combined with his chronic arm trouble the disease began to sap Hunter's energy. Following the 1979 season and the end of his five-year contract, Hunter retired from baseball at age 33. Hunter won 63 games in his five seasons with the Yankees.
He returned to his farm in Hertford where he grew soybeans, corn, peanuts, and cotton, and was a spokesman for diabetes awareness. Hunter noticed arm weakness while hunting in the winter of 1997-1998. He was diagnosed with amyotrophic lateral sclerosis (ALS).
Hunter died at his home in Hertford in 1999 at age 53. He died a year after being diagnosed with ALS. A month before his death, Hunter fell and hit his head on concrete steps at home. He was unconscious for several days after the fall, but he had returned home from that hospitalization when he died. Hunter is interred at Cedarwood Cemetery in Hertford, adjacent to the field where he played high school baseball.
In 1976, Hunter became the fourth major league pitcher to win 200 games before the age of 31 and the only one since Walter Johnson in 1915, preceded by Cy Young and Christy Mathewson. Hunter was also a competent hitter, with a career batting average of .226; in 1971 he hit .350 with 36 hits in 38 games. After the designated hitter was adopted by the American League in 1973, Hunter had only two plate appearances in his final seven seasons, with one base hit in 1973.
Along with Billy Williams, Hunter was inducted into the National Baseball Hall of Fame in Cooperstown in 1987. At the time, a player was allowed to choose which team's cap would be memorialized on his Hall of Fame Plaque. Before and after his induction, Hunter spoke highly of his experiences with both the Athletics and Yankees and his appreciation for both team owners, Charlie Finley and George Steinbrenner. For this reason, he refused to choose a team and thus the plaque depicts him with no insignia on the cap. He was credited by Steinbrenner as the cornerstone of the Yankees in their return to championship form.
After Hunter's death, former teammate Reggie Jackson described Hunter as a "fabulous human being. He was a man of honor. He was a man of loyalty." Steinbrenner said, "We were not winning before Catfish arrived... He exemplified class and dignity and he taught us how to win." Former teammate Lou Piniella said, "Catfish was a very unique guy. If you didn't know he was making that kind of money, you'd never guess it because he was humble, very reserved about being a star-type player... almost a little bit shy. But he told great stories. He had a heck of a sense of humor. When you play with guys like that, you feel blessed."
Hunter has been the subject of multiple popular culture references. Bob Dylan wrote the song "Catfish" in 1975. the song was later released by Dylan, Joe Cocker and Kinky Friedman. In 1976, Hunter was also the subject of the Bobby Hollowell song "The Catfish Kid (Ballad of Jim Hunter)", which was performed by Big Tom White and released on a 45 RPM single. Hollowell was best friends with the young Jim Hunter while they grew up together.
Hunter is mentioned in the 1976 film The Bad News Bears. When Coach Morris Buttermaker (Walter Matthau) is trying to get Amanda Whurlitzer (Tatum O'Neal) to pitch for his Little League team, Amanda makes a number of outlandish demands (such as imported jeans, modeling school and ballet lessons) as conditions for joining the team. Buttermaker asks, "Who do you think you are, Catfish Hunter?" Amanda responds by asking, "Who's she?" In the movie Grumpier Old Men, an enormous and highly prized fish is named "Catfish Hunter" by the locals. In You, Me and Dupree, Catfish Hunter is mentioned by Owen Wilson's character, Dupree, convincing an Asian orchestra student that he can pitch: "First, call me Dupree 'cause I'm your teammate. Second, so what if you're in the orchestra? So was Catfish Hunter."
Minor-league pitcher Jason Kosow portrayed Hunter in the ESPN miniseries The Bronx is Burning, which depicted the 1977 New York Yankees.
The Jim "Catfish" Hunter Memorial is located in Hertford. An annual softball event is held in Hertford in memory of Hunter. All proceeds from the weekend benefit ALS research. The tournament has raised over $200,000 since 1999.