Cale's manager Mike Kappus said the performer and producer died Friday night of a heart attack at a hospital in La Jolla, Calif.
Born John Weldon Cale, the Oklahoma City-native influenced some of the most famous musicians in the 1970s with songs that were laid back and mellow, yet imbued with a driving groove.
Neil Young, Mark Knopfler and Bryan Ferry are among his many fans in the music world.
Cale was a former member of the Grand Ole Opry touring company, but he never rose to the level of success of his admirers, but his fingerprints could be heard all over the genre in the 70s, and his music remains influential.
His album with Clapton "The Road to Escondido" won a Grammy for Best Contemporary Blues Album in 2007. Clapton also recorded Cale's "Cocaine," ''Travelin' Light" and "I'll Make Love To You Anytime."
Artists including Santana, The Allman Brothers and Johnny Cash have all covered Cale's songs.
Cale was asked on his website if it bothers him that "contemporaries and critics list him amongst legends, and fans might love his songs yet not even know his name?"
"No, it doesn't bother me," he said with a laugh. "What's really nice is when you get a check in the mail."
The Associated Press contributed to this report.