After the war, Sweetwater Clifton joined the New York Rens, an all-black professional basketball team that toured throughout the United States. Noted for his large hands, which required a size 14 glove, he was invited to join the Harlem Globetrotters, for whom he played from the summer of 1948 to the spring of 1950. Still a talented baseball first baseman, during the basketball off-season in 1949 Clifton played for the Chicago American Giants in Negro League baseball. By 1950, his performance with the Globetrotters, in particular his exceptional ball-handling ability, led to his signing a contract with an NBA team.
In 1957, Clifton was part of a multi-player trade between the Knicks and the Detroit Pistons, but after one season in Detroit he retired from basketball. In the summer of 1958, he joined the Detroit Clowns baseball team in the Negro Leagues, along with his former Harlem Globetrotters teammate Reece "Goose" Tatum.
In 1961, he was coaxed out of retirement by the Chicago Majors of the fledgling American Basketball League (ABL). After the league folded at the end of 1962, the 40-year-old Clifton retired permanently.
Clifton, who played softball for the Brown Bombers and Capitol Records team of the "Daddy O" Daylie League, was also inducted into Chicago 16 Inch Softball Hall of Fame.
On his death in 1990, Sweetwater Clifton was interred in the Restvale Cemetery in the Chicago suburb of Alsip.