By his mid-teens Leonard proved adept at boxing, and, as an amateur, he won 145 of 150 bouts and garnered two National Golden Glove championships (1973, 1974), two Amateur Athletic Union championships (1974, 1975), and a gold medal at the 1975 Pan American Games. Following his Olympic victory in 1976, he announced his retirement from the sport but reentered the ring as a professional on February 5, 1977.

In November 1979 Leonard defeated the reigning World Boxing Council (WBC) welterweight champion, Wilfred Benítez, only to lose the title in June 1980 in a famous match against Roberto Durán. Five months later Leonard regained the title by defeating Durán, and he successfully defended it thereafter, winning the World Boxing Association (WBA) version of the title with a victory over Thomas Hearns in 1981. Earlier that same year he had won the WBA junior-middleweight title with a ninth-round knockout of Ayub Kalule.

Leonard retired from prizefighting in 1982 and again in 1984 but was enticed to return in April 1987 to face the up-and-coming Marvelous Marvin Hagler (Hagler, Marvin), whom he defeated to capture the WBC middleweight title in what was considered one of the greatest professional boxing matches of all time.

Leonard retired again in 1991 after losing a WBC super welterweight title bout, but he returned to the ring once more in 1997, at age 40, and lost by a fifth-round technical knockout. He retired after the fight and was inducted into the International Boxing Hall of Fame later that year. After his final retirement, Leonard served as a boxing commentator and television host.