Brown was born on May 3, 1933, in Barnwell, South Carolina, to 16-year-old Susie (nee Behling, 1917-2003) and 22-year-old Joseph Gardner Brown (1911-1993), in a small wooden shack. Brown's name was supposed to have been Joseph James Brown, but his first and middle names were mistakenly reversed on his birth certificate. He later legally changed his name to remove "Jr." His parents were both African-American; in his autobiography, Brown stated that he also had Chinese and Native American ancestry.

On December 23, 2006, Brown became very ill and arrived at his dentist's office in Atlanta, Georgia, several hours late. His appointment was for dental implant work. During that visit, Brown's dentist observed that he looked "very bad... weak and dazed." Instead of performing the work, the dentist advised Brown to see a doctor right away about his medical condition. Brown went to the Emory Crawford Long Memorial Hospital the next day for medical evaluation and was admitted for observation and treatment. According to Charles Bobbit, his longtime personal manager and friend, Brown had been struggling with a noisy cough since returning from a November trip to Europe. Yet, Bobbit said, the singer had a history of never complaining about being sick and often performed while ill. Although Brown had to cancel upcoming concerts in Waterbury, Connecticut, and Englewood, New Jersey, he was confident that the doctor would discharge him from the hospital in time for his scheduled New Year's Eve shows at the Count Basie Theatre in New Jersey and the B. B. King Blues Club in New York, in addition to performing a song live on CNN for the Anderson Cooper New Year's Eve special. Brown remained hospitalized, however, and his condition worsened throughout the day. On Christmas Day, 2006, Brown died at approximately 1:45 am EST (06:45 UTC), at age 73, from congestive heart failure, resulting from complications of pneumonia. Bobbit was at his bedside and later reported that Brown stuttered, "I'm going away tonight," then took three long, quiet breaths and fell asleep before dying.

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Bobbit was at his bedside and later reported that Brown stuttered, "I'm going away tonight," then took three long, quiet breaths and fell asleep before dying.