Born in White Station near West Point, Mississippi, he was named after Chester A. Arthur, 21st President of the United States, and was nicknamed Big Foot Chester and Bull Cow in his early years because of his massive size. He explained the origin of the name Howlin` Wolf thus: "I got that from my grandfather [John Jones]." He used to tell him stories about the wolves in that part of the country and warn him that if he misbehaved, they would "get him". As a youth he listened to Charley Patton, who taught him the rudiments of guitar, as well as to the Mississippi Sheiks, Tommy Johnson, and Jimmie Rodgers, whose famous "blue yodel" Burnett integrated into his singing style. His harmonica playing was modeled after that of Rice Miller (also known as Sonny Boy Williamson II), who had lived with his sister for a time and taught him how to play. He played with Robert Johnson and Willie Brown in his youth.

He farmed during the 1930s, served in the United States Army as a radioman in Seattle during World War II, and by 1948 had formed a band which included guitarists Willie Johnson and M. T. Murphy, harmonica player Junior Parker, a pianist remembered only as "Destruction", and drummer Willie Steele. He began broadcasting on KWEM in West Memphis, Arkansas, alternating between performing and pitching farm equipment, and auditioned for Sam Phillips`s Memphis Recording Service in 1951.

According to the documentary film The Howlin` Wolf Story, Howlin` Wolf`s parents broke up when he was young. His very religious mother Gertrude threw him out of the house for refusing to work around the farm while still a child; he then moved in with his uncle, Will Young, who treated him badly. When he was 13, he ran away and claimed to have walked 85 miles barefoot to join his father, where he finally found a happy home within his father`s large family. During the peak of his success, he returned from Chicago to his home town to see his mother again, but was driven to tears when she rebuffed him and refused to take any money he offered her, saying it was from his playing the "Devil`s music".

Howlin` Wolf quickly became a local celebrity, and soon began working with a band that included both Willie Johnson and guitarist Pat Hare. His first recordings came in 1951, when he recorded sessions for both the Bihari brothers at Modern Records and Leonard Chess` Chess Records. Chess issued Howlin` Wolf`s How Many More Years in August 1951; Wolf also recorded sides for Modern, with Ike Turner, in late 1951 and early 1952. Chess eventually won the war over the singer, and Wolf settled in Chicago, Illinois c. 1953. Upon arriving in Chicago, he assembled a new band, recruiting Chicagoan Joseph Leon "Jody" Williams from Memphis Slim`s band as his first guitarist. Within a year Wolf enticed guitarist Hubert Sumlin to leave Memphis and join him in Chicago; Sumlin`s terse, curlicued solos perfectly complemented Burnett`s huge voice and surprisingly subtle phrasing. Although the line up of Wolf`s band would change regularly over the years, employing many different guitarists both on recordings and in live performance including Willie Johnson, Jody Williams, Lee Cooper, L.D. McGhee, Otis "Big Smokey" Smothers, his brother Abe "Little Smokey" Smothers, Jimmy Rogers, Freddie "Abu Talib" Robinson, and Buddy Guy, among others, with the exception of a couple of brief absences in the late `50s Sumlin remained a member of the band for the rest of Wolf`s career, and is th