After a failed early solo career, Zevon spent time as a session musician (notably as piano player for the Everly Brothers) and jingle composer. In the mid-70s, he moved to Los Angeles and became associated with the then-burgeoning West coast music scene, including collaborations with Jackson Browne, who would produce and promote Zevon's self-titled major-label debut, and Linda Ronstadt, who would record several early Zevon songs including a hit version of "Poor Poor Pitiful Me".
In 1978 Zevon released his breakthrough album, Excitable Boy, to critical acclaim and popular success. Several tracks from this album received heavy FM airplay and the single release "Werewolves of London", which featured a relatively lighthearted version of Zevon's signature macabre outlook, was a top-ten hit.
For the next 20 years Zevon would continue to record and release albums sporadically and with varying levels of success, while fighting personal demons including an acknowledged battle with alcoholism. He also collaborated with several members of R.E.M. to record as the Hindu Love Gods in 1990.
In interviews, Zevon described a lifelong phobia of doctors and seldom received medical assessment. In 2002, after a long period of untreated illness and pain, Zevon was encouraged by his dentist to see a doctor; when he did so he was diagnosed with inoperable mesothelioma (a form of lung cancer). He then began recording his final album, The Wind, with guest appearances from close friends including Bruce Springsteen, Don Henley, Timothy B. Schmidt, Joe Walsh, David Lindley, Billy Bob Thornton, Emmylou Harris, and others.
On October 30, 2002, Zevon was featured on the Late Show with David Letterman as the only guest for the entire hour. Zevon performed several songs and spoke in length about his illness. Zevon was a frequent guest and occasional substitute bandleader on Letterman's television shows since Late Night first aired in 1982.
Zevon had previously stated that his illness was expected to be terminal within months after the diagnosis in the Fall of 2002; however he lived to see the release of The Wind on August 28, 2003 and the birth of twin grandsons in June of 2003.
Zevon died at his home on September 7, 2003. The Wind was certified gold (sales in excess of 500,000 copies) by the RIAA in December 2003, & Zevon received 5 posthumous Grammy nominations (including Song Of The Year for "Keep Me In Your Heart").