His spokeswoman, Schatzie Hageman, says Jennings passed peacefully at his Arizona home.
Jennings' health had been waning since the mid-'80s, when he underwent heart surgery (sharing a hospital room with longtime partner in crime and fellow heart patient Johnny Cash). He was later diagnosed with diabetes, which drastically affected his circulation, making it difficult for him to walk in recent years. In December, his left foot was amputated after becoming infected.
"Waylon was a dear friend, one of the very best of 35 years," Cash said Wednesday. "I'll miss him immensely."
Singer and friend Kris Kristofferson called Jennings "an American archetype, the bad guy with a big heart."
Born in Littlefield, Texas, in 1937, he formed his first band at the age of 12. By the time he was 17, he was deejaying a few towns away in Lubbock, where he hooked up with local boy Buddy Holly. Holly soon took Jennings under wing, teaching the younger musician some guitar chords and producing Jennings' first single, "Jole Blon," and cowriting "You're the One."
Jennings filled in on bass for the Crickets during Holly's final tour in 1958-59. In fact, Jennings was supposed to join Holly and Ritchie Valens on their ill-fated flight, but he gave up his seat moments before depature to the Big Bopper (aka J.P. Richardson), who had come down with a cold and didn't want to travel by tour bus. The plane crashed in a driving snowstorm, killing all aboard.
After the crash, Jennings' career progressed fitfully, as he refused to be pigeonholed as an overproduced Nashville slickster or as a straight pop singer. He jumped from A&M Records to RCA in 1965, where he worked as a session player and began turning out the sparse, alt-country tunes that became his trademark. He cranked out such hits as "Stop the World (and Let Me Off)," "Walk on Out of My Mind," "I Got You," "Only Daddy That'll Walk the Line," "This Time," "I'm a Ramblin' Man," "Rainy Day Woman," "Are You Sure Hank Done It This Way," "The Wurlitzer Prize (I Don't Want to Get Over You)," "Luckenbach, Texas," "I've Always Been Crazy" and "Amanda." All told he had 16 number-one country singles.
He won his first Grammy in 1969 for his collaboration with the Kimberlys on "MacArthur Park."
During the '60s he roomed with Cash in Nashville, and the two remained close for the rest of Jennings' life. He also struck up a songwriting and recording partnership with Willie Nelson. That pairing produced one of Jennings' best-known tunes, "Mammas, Don't Let Your Babies Grow Up to Be Cowboys," a chart-topping hit in 1978 that earned the duo a Grammy.
Jennings also found fame on the small screen, as the ballad-singing narrator on The Dukes of Hazzard. His classic theme song was a top 40 hit and million-seller.
Throughout his five-decade, 60-plus-album career, Jennings steadfastly refused to join the Nashville mainstream, however, and became a posterboy for the outlaw movement, whose adherents were known for their uncompromising music, dark clothes, black hats and scraggly appearance.
He teamed with fellow antiheroes Cash, Nelson and Kristofferson to form the Highwaymen, an occasional supergroup that turned out three albums, some TV movies (including Stagecoach and Outlaw Justice) and the chart-topping single, "Highwayman."
Jennings also lived the two-fisted outlaw life. He had a nasty, $1,500-a-day cocaine habit that he finally managed to kick, cold-turkey, in the 1980s.
Although dogged by ill-health and erratic chart success in later years, Jennings still made the rounds on the concert circuit and was scheduled for a tour in the spring. Jennings was enshrined in the Country Music Hall of Fame in October but, in typical style, refused to attend.
He was married four times and is survived by his wife of 32 years, singer Jessi Colter, and their son, Shooter.