Clark was born in Tulsa, Oklahoma, but was raised in Phoenix, Arizona, from the age of 9. He first began performing in the Phoenix area in the early 1950s. He spent time in the Air Force in the South Pacific; he formed a band there which won a talent show in Hawaii. Returning to Phoenix, he and his friend Al Casey met Lee Hazlewood, then a local DJ. Clark, with Casey on guitar, recorded one of Hazlewood's songs, "The Fool", on MCI Records in 1956. Dot Records picked the song up for national distribution after a Philadelphia deejay tipped them off to it. The song became a hit in the U.S., peaking at No. 14 on the Country Singles chart, No. 5 on the Black Singles chart, and No. 7 on the Billboard Top 100. Following the song's success, Clark opened on tour for Ray Price and Roy Orbison.
Clark's 1957 follow-up single, "The Cheat", gave him a second minor hit, peaking at No. 74 Pop. He and Dot Records' owner Randy Wood quarreled over the singer's image, and he eventually signed to Jamie Records in 1958, continuing to work with Hazlewood. In 1959 Sanford Clark recorded a song, "Son of a Gun", about the son of a western gunslinger. This song is also referenced in Keith Richards' book life published in October 2010. He credits the song as being one of the first song he learned and performed on stage prior to forming the Rolling Stones.
Moving to Hollywood, he recorded for several other labels and had several almost-comebacks; his 1964 version of Hazlewood's "Houston" was eclipsed by Dean Martin's version, and in 1965 he re-recorded "The Fool" with Waylon Jennings on guitar. Hazlewood, by now an established songwriter, signed Clark to his own label, LHI, on which Clark released The Black Widow b/w The Son of Hickory Holler's Tramp in 1967, Farm Labor Camp #2 and the album Return of the Fool in 1968.
A few years later Clark left the music business, working in construction, though he occasionally recorded in later decades on his own label, Desert Sun Records.
"The Fool" has been recorded by Chris Farlowe (1965 single), Elvis Presley for Elvis Country (I'm 10,000 Years Old) (1971), The Animals for Before We Were So Rudely Interrupted (1977) and by Richard Thompson on 1000 Years of Popular Music (live) among many others.