Byrd helped shape much of the nation's history and served a dozen US presidents. He died peacefully at Inova Fairfax Hospital outside Washington, DC, said his spokesman, Jesse Jacobs. Mr Byrd was hospitalised last week with what doctors believed was a heat-related illness.
"I love to serve. I love the Senate. If I could live another 100 years, I'd like to continue in the Senate," Mr Byrd, who kept a copy of the US Constitution in his breast pocket, said in a 2006 interview.
Senator Jay Rockefeller, also of West Virginia, said: "Senator Byrd came from humble beginnings in the southern coalfields … and triumphantly rose to the heights of power in America. But he never forgot where he came from, nor who he represented, and he never abused that power for his own gain."
Mr Byrd was first elected to the House of Representatives in 1952, and served six years in that chamber before moving to the Senate. His early campaigns were punctuated by his skills as a bluegrass fiddler that helped draw big and enthusiastic crowds for the self-described West Virginia "hillbilly".
With his old-fashioned courtliness, Mr Byrd was a defender of the Senate's traditions and over the years held many key positions, including Democratic leader from 1977-1988 and also the top Democrat on the powerful Appropriations Committee.
Mr Byrd was an early opponent of the Iraq War, which began in 2003 with popular support but within a few years was widely condemned. He also warned against a build-up of US troops in Afghanistan.
He worked with and challenged presidents, Democrat and Republican alike, and reminded all of them of Congress' responsibility to check their power.
"I'm not any president's man. I'm a Senate's man," Mr Byrd once said.
During his more than half-century in Congress, America changed dramatically and so did Mr Byrd.
In the early 1940s, before being elected to Congress, Mr Byrd belonged to the Ku Klux Klan, a membership that he attributed to a youthful mistake.
"It has emerged throughout my life to haunt and embarrass me and has taught me in a very graphic way what one major mistake can do to one's life, career and reputation," Mr Byrd wrote in a 1987 memoir, Robert C Byrd: Child of the Appalachian Coalfields.
In Congress, Mr Byrd, who denounced civil rights leader Martin Luther King as a "self-seeking rabble rouser", eventually became a leading backer of civil rights.
MUCH-LOVED 'PRINCE OF PORK'
OF THE 18,500-plus Senate votes Byrd cast, he said his biggest regret was opposing the 1964 Civil Rights Act, a landmark law that brought down barriers for black Americans.
He said his views changed most dramatically after his teenage grandson was killed in a 1982 traffic accident.
He said: "The death of my grandson caused me to stop and think. I came to realise that black people love their children as much as I do mine."
In West Virginia, Byrd was revered for his ability to deliver federal dollars to his poor state to build roads, schools and hospitals. Critics called him the "Prince of Pork" but constituents crowned him "West Virginian of the 20th century".