Percy Sledge worked in a series of blue-collar jobs in the fields in Leighton, Alabama before taking a job as an orderly at Colbert County Hospital in Sheffield, Alabama. Through the mid 1960s, he toured the Southeast with the Esquires Combo on weekends, while working at the hospital during the week. A former patient and mutual friend of Sledge and record producer Quin Ivy introduced the two. An audition followed, and Sledge was signed to a recording contract.

Sledge's soulful voice was perfect for the series of soul ballads produced by Ivy and Marlin Greene, which rock critic Dave Marsh called "emotional classics for romantics of all ages."

"When a Man Loves a Woman" was Sledge's first song recorded under the contract, and was released in March 1966. The song's inspiration came when Sledge's girlfriend left him for a modeling career after he was laid off from construction job in late 1965. Because bassist Calvin Lewis and organist Andrew Wright helped him with the song, he gave all the songwriting credits to them.[4] It reached #1 in the U.S. and went on to become an international hit. "When A Man Loves A Woman" was a hit twice in the UK, reaching #6 in 1966 and, on reissue, peaked at #2 in 1987. The song was also the first gold record released by Atlantic Records. the soul anthem became the cornerstone of Sledge's career, and was followed by "Warm and Tender Love" (Covered by UK songstress Elkie Brooks in 1981), "It Tears Me Up", "Take Time to Know Her" (his second biggest U.S. hit, reaching #11), "Love Me Tender", and "Cover Me".
Sledge charted with "I'll Be Your Everything" and "Sunshine" during the 1970s, and has become an international concert favorite throughout the world, especially in the Netherlands, Germany, and on the African continent, and South Africa in particular.