Fosse's career was marked by injuries. He made his Major League debut in Cleveland late in the 1967 season, but spent 1968 in the minor leagues. Returning to the Indians in 1970, he platooned alongside Duke Sims. In the first half of 1970 he posted a .313 batting average with 16 home runs and 45 runs batted in. He hit in 23 consecutive games beginning June 9, the longest American League hitting streak since 1961, and was chosen as a reserve for the 1970 All-Star Game by Earl Weaver, the American League manager.
Arguably, Fosse is best known for a violent collision with Pete Rose at home plate during the last play of the 1970 All-Star Game. Initial x-rays revealed no fractures or other damage, but a re-examination the following year found that Fosse had sustained a fractured and separated shoulder, which healed incorrectly, causing chronic pain that never entirely resolved. Rose asserted that he was simply trying to win the game, and that Fosse — who had moved a few feet up the third-base line to receive the throw from Amos Otis — was blocking the plate; but Rose was widely criticized for over-aggressive play in an exhibition game. Fosse went on to play 42 games in the second half of the season, hitting .297 and winning the American League Gold Glove Award.
In 1971 Fosse batted .276 with 12 home runs and 62 runs batted in, but was kicked in his right hand during a brawl against the Detroit Tigers on June 20, sustaining a gash that required five stitches and sidelined him for more than a week. When he returned he tore a ligament in his left hand during an at-bat against Denny McLain, forcing him to miss the 1971 All-Star Game. He did manage to win his second consecutive Gold Glove Award. When Cleveland pitcher Gaylord Perry won the American League Cy Young Award in 1972, he gave Fosse credit for his success: "I've got to split it up and give part, a big part, to my catcher, Ray Fosse. He kept pushing me in games when I didn't have good stuff. He'd come out and show me that big fist of his when I wasn't bearing down the way he thought I should."
In 1973 Fosse was traded along with Jack Heidemann to the Oakland Athletics for Dave Duncan and George Hendrick. He played in 143 games that season, the most of his career, on a team with three 20-game-winning pitchers: Ken Holtzman, Vida Blue, and Catfish Hunter. The Athletics won the American League Western Division pennant by six games over the Kansas City Royals, then defeated the Baltimore Orioles in the American League Championship Series. Fosse made his mark in the series, throwing out five would-be base stealers. The Athletics went on to win the World Series against the New York Mets.
The Athletics repeated as world champions in 1974, defeating the Los Angeles Dodgers in the World Series, but injuries once again plagued Fosse. On June 5 he suffered a crushed disk in his neck attempting to break up a clubhouse fight between teammates Reggie Jackson and Billy North, and spent three months on the disabled list. The Athletics won a fifth consecutive division title in 1975, but by then Gene Tenace had replaced Fosse as the starting catcher. Fosse did participate in a combined no-hitter in the final game of the season, catching for Paul Lindblad and Rollie Fingers in the final three innings.
The Athletics traded Fosse back to the Indians in 1976 where he again became the starting catcher, only to return to the disabled list after a home plate collision with Jim Rice. When he returned he was platooned with Alan Ashby. Fosse ended the year with a .301 batting average. On May 30, 1977, he caught Dennis Eckersley's no-hitter versus the California Angels. Eckersley acknowledged Fosse's contribution to the no hitter: "Give Fosse a lot of credit too," he said. "He called a helluva game. I think I only shook him off three times." When Jeff Torborg replaced Frank Robinson as manager of the Indians in June 1977, he again placed Fosse in a platoon role with Fred Kendall. In September he was traded to the Seattle Mariners.
After finishing the year with the Mariners he signed a contract to play for the Milwaukee Brewers; but during spring training he tripped in a hole while running down the first base line and sustained injuries to his right leg. The most serious injury required the reconstruction of a knee ligament, forcing him to miss the entire season. He came back in 1979 but played in only 19 games; in 1980 he was released at the close of spring training.
In a twelve-year major league career, Fosse played in 924 games, accumulating 758 hits in 2,957 at bats for a .256 career batting average along with 61 home runs and 324 runs batted in. He ended his career with a .986 fielding percentage. Fosse led American League catchers in 1970 with 854 putouts, 48 baserunners caught stealing and in range factor (7.81). In 1971 he led the league with 73 assists, and in 1973, he led American League catchers in baserunners caught stealing and in caught stealing percentage.
Fosse was a member of two World Series Champion clubs: the 1973 and 1974 A's, and also a member of the inaugural Seattle Mariners team that began playing in 1977. He won Gold Glove Awards in 1970 and 1971. Fosse was named to the 100 Greatest Cleveland Indians in 2001.
Fosse is a color commentator for the Oakland Athletics on CSN California and occasionally on the A's radio broadcasts when the game is not on TV or is on national television. He has served as the color analyst for the Oakland Athletics' radio and television broadcasts since 1986. In 2002, he was nominated for a Ford C. Frick Award.
Fosse has been married to his wife Carol since April 1970. They maintain residences in Oakland, California and Scottsdale, Arizona.