Ron O'Neal grew up in a working-class neighborhood of Cleveland, Ohio, to the parents of Eunice and Ernest O'Neal a former jazz musician who earned his living as a factory worker; Ernest died when Ron was 16 years old. Only six months later his brother, who worked as a truck driver, was killed in an accident. Following these tragedies his mother found a job in a hospital to sustain the family. He graduated from Glenville High School, then attended Ohio State University, and there became interested in acting after seeing the play Finian's Rainbow. He joined the Karamu House company in Cleveland, Ohio, working with the oldest African-American theatre company in the United States from 1957 until 1964, during which period he appeared in plays such as Kiss Me, Kate, A Streetcar Named Desire and A Raisin in the Sun, while working as a housepainter to earn his living. In 1964, he went to New York, teaching acting classes at the Harlem Youth Arts Program and appearing in Off-Broadway plays.