"The people of West Virginia have lost a dedicated public servant, and America has lost a great defender of its most precious traditions," Reid said in a statement. "He was the foremost guardian of the Senate's complex rules, procedures and customs, and as leader of both the majority and the minority caucuses in the Senate he knew better than most that legislation is the art of compromise."
Senate Minority Leader Mitch McConnell, R-Kentucky, praised Byrd's "fighter's spirit" and "abiding faith."
"He was a great patriot. He loved the Senate, there's no doubt about it," Sen. Jeff Sessions, R-Alabama, said on "GMA." "He had a great way for words."
Under West Virginia law, if a the vacancy in the Senate occurs less than two years and six months before the end of the term -- which in this case is January 2013 -- the governor appoints someone to fill the entire term. But if a vacancy occurs before that time period, as would be the case with Byrd's death, a special election is held in November to fill the remainder of the term.
Manchin, whose second term expires in 2012, is said to be eyeing the seat himself.
In a written statement Monday morning, Manchin said all West Virginians' hearts break at the passing of Byrd and that the state has "suffered a terrible loss."
With Byrd's death, Democrats not only lost a longtime leader but also the crucial 60th vote to pass the financial reform bill that has been pending for weeks in the Senate.
During the Great Depression, Byrd graduated as valedictorian of his high school class but could not afford college. Instead, he sought employment wherever he found an opportunity -- whether it meant pumping gas, selling produce or working as a butcher.
Welding, one of the skills Byrd developed, was in demand after the beginning of World War II. During the war years, he helped build the USS Liberty and USS Victory. At war's end, in 1946, he returned to West Virginia with political aspirations and mounted a successful campaign for the West Virginia House of Delegates.
After serving two terms, Byrd was elected to the West Virginia Senate, then to the U.S. House of Representatives for three terms, and finally, in 1958, to the Senate. He has represented West Virginia continuously, winning re-election by record margins in statewide elections.
Despite his successful political track record, the Senate's senior Democrat was no stranger to controversy, and was once a member of the Ku Klux Klan.
Byrd said he joined the white supremacist group in 1942 because it "offered excitement." He claimed the Klan was an "effective force" in "promoting traditional American values" and "was strongly opposed to communism."
Byrd reportedly ended his ties with the group in 1943, telling the Washington Post in June 1993 that his stint in the KKK was the mistake in his life that he most regretted.
"Just as a lot of young people these days join organizations they regret joining, I joined as a youth and regretted it later," he said. "I made a mistake."