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Hawkins' most successful recording, "I Put a Spell on You" (1956), was selected as one of The Rock and Roll Hall of Fame's 500 Songs that Shaped Rock and Roll. According to the AllMusic Guide to the Blues, "Hawkins originally envisioned the tune as a refined ballad." The entire band was intoxicated during a recording session where "Hawkins screamed, grunted, and gurgled his way through the tune with utter drunken abandon." The resulting performance was no ballad but instead a "raw, guttural track" that became his greatest commercial success and reportedly surpassed a million copies in sales, although it failed to make the Billboard pop or R&B charts.
Although Hawkins himself blacked out and was unable to remember the session, he relearned the song from the recorded version. Meanwhile, the record label released a second version of the single, removing most of the grunts that had embellished the original performance; this was in response to complaints about the recording's overt sexuality. Nonetheless it was banned from radio in some areas. Furthermore, the recording attracted the ire of groups such as the NAACP, "which worried that his act would reflect badly on African Americans."Hawkins later credited the uproar with a boost in sales due to the perceived taboo nature of his performances.
Soon after the release of "I Put a Spell on You", radio disc jockey Alan Freed offered Hawkins $300 to emerge from a coffin onstage. Hawkins initially declined, reportedly saying "No black dude gets in a coffin alive – they don't expect to get out!" However, he later relented and soon created an outlandish stage persona in which performances began with the coffin and included "gold and leopard-skin costumes and notable voodoo stage props, such as his smoking skull on a stick – named Henry – and rubber snakes."[These props were suggestive of voodoo, but also presented with comic overtones that invited comparison to "a black Vincent Price."Despite the commercial success of the gimmick, Hawkins resented the schlock-factor that made him famous. He found it exploitative, and believed it undermined his sincerity as a vocalist and a balladeer. In a 1973 interview, he bemoaned the Screamin' epithet given to him by his label Okeh records, saying "If it were up to me, I wouldn't be Screamin’ Jay Hawkins...James Brown did an awful lot of screamin’, but never got called Screamin’ James Brown...Why can't people take me as a regular singer without making a bogeyman out of me?"
Hawkins performing in 1979.
"I Put a Spell On You" became a classic, covered by a variety of artists such as Creedence Clearwater Revival, Nina Simone, Alan Price, The Animals, Them with Van Morrison, Arthur Brown, Bryan Ferry, Buddy Guy, Carlos Santana, Tim Curry, Leon Russell, Joe Cocker, Nick Cave, Marilyn Manson, Mica Paris, David Gilmour, Jeff Beck, Joss Stone, Diamanda Galas, and Annie Lennox. Hawkins' original version was featured during the show and over the credits of the 2003 The Simpsons episode "I'm Spelling as Fast as I Can".