He was born Otha Ellas Bates in McComb, Mississippi and later took the name Ellas McDaniel, after his adoptive mother, Gussie McDaniel. He adopted the stage name Bo Diddley, which is probably a southern black slang phrase meaning "nothing at all," as in "he ain't bo diddley." Another source says it was his nickname as a Golden Gloves boxer. The nickname is also linked to the diddley bow, a one stringed instrument used in the south by mainly black musicians in the fields.

He is best known for the "Bo Diddley beat," a rhumba-based beat (see clave) also influenced by what is known as "hambone," a style used by street performers who play out the beat by slapping and patting their arms, legs, chest, and cheeks while chanting rhymes. The Bo Diddley beat is often illustrated with the phrase: "shave 'n' a haircut - two bits."

The beat has been used by many other artists, notably Johnny Otis on "Willie and the Hand Jive," which is more about hambone than it is a direct copy of Bo Diddley, Bruce Springsteen's "She's the One," U2's "Desire," Buddy Holly's "Not Fade Away" and Rolling Stones' "Mona" as well as more obscure numbers such as "Callin' All Cows" by The Blues Rockers.

Bo Diddley died on June 2, 2008 at the age of 79 of heart failure at his home in Archer, Florida. Garry Mitchell, a grandson of Diddley and one of more than 35 family members at the musician's home when he died at about 1:45 a.m., said his death was not unexpected. "There was a gospel song that was sung and he said 'wow' with a thumbs up," Mitchell told Reuters, when asked to describe the scene at Diddley's deathbed. "The song was 'Walk Around Heaven' and in his last words he said that he was going to heaven."