Cale's website said he died of a heart attack Friday at Scripps Memorial Hospital.
As a singer, Cale had a hit in 1972 with "Crazy Mama," but his greatest success came as the writer of such hits as "Cocaine" and "After Midnight" for Clapton and "Call Me The Breeze" for Lynyrd Skynyrd.
When Clapton covered "After Midnight," Cale, in his early 30s, had resigned himself to making a living some other way. He was living in Tulsa, Okla., but the success encouraged him to go to Nashville to make his first album, CNN reported.
He won a Grammy in 2007 for Best Contemporary Blues Album, "The Road to Escondido," which he made with Clapton.
His work was also covered by The Band, Maria Muldaur and Captain Beefheart, among others.
Cale was once asked if he minded being unknown to the general public.
"No, it doesn't bother me," Cale said. "What's really nice is when you get a check in the mail."