Born in Manhattan, New York City, and raised in nearby Mount Vernon, Singleton played both baseball and basketball in high school. He also played baseball in the Bronx Federation League at Macombs Dam Park, across the street from Yankee Stadium. Singleton was drafted out of Hofstra University by the New York Mets as the third overall pick in the 1st round of the 1967 Major League Baseball draft. He made his major league debut with the Mets on June 24, 1970 at the age of 23. In April 1972, he was part of a package traded to the Montreal Expos for Rusty Staub.

Singleton's best year of the three in Montreal was 1973, when he led the league in on-base percentage (one of nine top-ten finishes in that category over the course of his career) and collected 23 home runs, 103 RBIs and a .302 batting average (his first .300 season).

Singleton was acquired along with Mike Torrez by the Baltimore Orioles from the Expos in exchange for Dave McNally, Rich Coggins and pitcher Bill Kirkpatrick on December 4, 1974. During his ten years in Baltimore, Singleton played the best baseball of his career as the Orioles won two pennants, in 1979 and 1983, and won the 1983 World Series. In 1977, he posted a career-high .328 batting average, third highest in the American League. In 1979 he had career-highs with 35 home runs and 111 RBIs. Singleton played in his final major league game on September 25, 1984, at the age of 37.

In a fifteen-year major league career, Singleton played in 2,082 games, accumulating 2,029 hits in 7,189 at bats for a .282 career batting average along with 246 home runs, 1,065 runs batted in and an on-base percentage of .388. He had a career .980 fielding percentage. Singleton ranks among the Orioles all-time Leaders in numerous offensive statistics. An All-Star in 1977, 1979 and 1981, he won the Roberto Clemente Award in 1982. His highest finish in the Most Valuable Player Award balloting was in 1979, when he finished second to Don Baylor. He was third in 1977, behind Al Cowens and the winner, Rod Carew.

After retiring as a baseball player, Singleton began his broadcasting career as a Sportscaster for WJZ-TV in Baltimore in the middle 1980s and TSN in Canada, first as a color commentator on telecasts for the Toronto Blue Jays (1985 and 1986) and then as a television color commentator and as a radio play-by-play and color commentator for the Montreal Expos (1987 to 1996).

In the 1986 edition of the Bill James Historical Baseball Abstract, James' wife Susan McCarthy picked Ken Singleton as one of the best-looking players in the 1970s. In a subsequent edition, James wrote that, upon reading the entry, Singleton sent her a thank-you card.

Currently, Singleton is a commentator for the New York Yankees on the YES Network, serving as both a color commentator and play-by-play announcer, along with partner and play-by-play announcer Michael Kay. He also worked as an announcer for Yankee games on the MSG Network, before the inception of YES and joined the Yankees broadcasting team in 1997.

On March 12, 2018, Singleton announced that he would be leaving the broadcasting booth, effective after the 2018 season.