By the age of four, Hines and his older brother Maurice were taking tap lessons with renowned dancer and choreographer Henry Le Tang. The brothers soon formed the Hines Kids, a song-and-dance act that appeared in clubs across the United States. When Gregory was six years old the duo performed at the Apollo Theater in New York, and two years later he made his Broadway debut in The Girl in Pink Tights (1954). The act's name was later changed to the Hines Brothers, and in 1963 it became Hines, Hines and Dad when their father joined them as a drummer. The trio made numerous television appearances and performed throughout the United States and Europe. Mounting tensions with his brother, however, and declining public interest in tap dancing led Gregory to leave the act in 1973 and move to California. There he formed the jazz-rock band Severance, serving as songwriter, singer, and guitarist. By the late 1970s, however, the band had broken up, and Hines had returned to New York to resume his dancing career.

In 1978 Hines starred with his brother in Eubie!, a tribute to American ragtime pianist and composer Eubie Blake (Blake, Eubie) that was choreographed by Le Tang. The production was a great success and sparked new interest in tap dancing. Hines received a Tony Award nomination, and other nominations followed for performances in Comin' Uptown (1979) and Sophisticated Ladies (1981). In the early 1980s Hines began appearing regularly on television and in movies. He proved a versatile actor, and his numerous film credits include History of the World: Part I (1981), The Cotton Club (1984), and White Nights (1985), in which he starred with Mikhail Baryshnikov (Baryshnikov, Mikhail). In the 1989 film Tap, he appeared alongside Sammy Davis, Jr. (Davis, Sammy, Jr.), and other once well-known African American tap dancers. In 1989 he also won an Emmy Award for his television special Gregory Hines: Tap Dance in America. Hines continued to appear on Broadway, and in 1992 he costarred with Savion Glover (Glover, Savion) in Jelly's Last Jam. Portraying an older version of Jelly Roll Morton (Morton, Jelly Roll), Hines received his first Tony Award. He later performed in the role of dancer Bill “Bojangles” Robinson (Robinson, Bill) in the television film Bojangles (2001). In addition to his acting and dancing work, Hines also released an album of songs in 1988 and made his directorial debut with the 1994 film Bleeding Hearts.