Charles was born in Georgia in 1921 but came to Cincinnati at the age of nine to live with his grandmother and great-grandmother in the West End. He started his amateur boxing career in his teen years and won 42 amateur fights as a welterweight and a middleweight. In 1939 he won the Amateur Athletic Union national middleweight title. He graduated from Woodwoard High School in 1942.
Charles began his professional boxing career in March 1940 and fought 38 matches over the next three years. He won 33, lost four and had one draw. Twenty one of his 33 victories were by knockouts. Twenty-two of his 38 matches were held in Cincinnati. Charles served in the military in 1944 and 1945. In February 1946 Charles once again was back in the ring, now in the light heavyweight division.
In 1949 Charles moved up to the heavyweight division. On June 22, 1949 he defeated Jersey Joe Walcott to win the National Boxing Association championship. On September 28, 1950 he won a 15 round decision over Joe Louis and was proclaimed the world heavyweight champion. He successfully defended his title in three matches in 1951 but then lost his crown to Walcott in a re-match on July 18. From February 18, 1946 to July 18, 1951, Charles fought 42 matches and lost only twice. Out of his 40 victories in these years, he won 24 by knockouts.
Charles continued to box until 1959. From October 1951 through October 1956, he won 19 matches and lost 15. Ten of his victories were by KOs but he was also knocked out three times. In 1957 Charles retired from boxing only to return to fight six more times in 1958 and 1959. He lost four of his last six matches, two of those by KOs. Over the course of his professional boxing career, Ezzard Charles had 122 bouts with 95 wins, 25 losses and one draw.
Charles tried several jobs after the end of his boxing days. He was a safety inspector for the Sate of Ohio and then a bouncer at a Northern Kentucky nightclub. He tried professional wrestling using the name "Cincinnati Cobra." He moved to Chicago and in 1967 was working for Youth Welfare. He was diagnosed with amyotrophic lateral sclerosis and dies in 1975. In 1976 Cincinnati recognized Ezzard Charles by changing Lincoln Park Drive to Ezzard Charles Drive. In 1949 when he won the heavyweight championship, Charles lived at 929 Lincoln Park Drive. In 1990 Ezzard Charles was inducted into the International Boxing Hall of Fame.