In 1989, after 30 years of membership, he chaired the powerful Senate Appropriations Committee. That same year, he was unanimously elected president pro tempore of the Senate, a post that placed him third in the line of succession to the presidency. It also earned him the distinction of having the most leadership positions in the Senate.
In June 2001, Byrd regained the chairmanship of the Senate Appropriations Committee and was re-elected president pro tempore of the Senate.
Byrd was a fierce opponent of the Iraq War even though he supported the war in Vietnam. Byrd delivered a strongly worded rebuke of President George W. Bush, after he had received a vote of support from Congress.
"Today I weep for my country," Byrd said. "I have watched the events of recent months with a heavy, heavy heart. No more is the image of America one of strong, yet benevolent peacekeeper. The image of America has changed. Around the globe, our friends mistrust us, our word is disputed, our intentions are questioned."
Never consumed by the unrelenting demands of his job, Byrd was personal friends with many of his colleagues.
When Sen. Ted Kennedy suffered a seizure at a luncheon following Obama's inauguration, Byrd was so upset and distraught from what he had witnessed that he needed to be taken out of the Capitol Rotunda.
Late last year, despite being confined to a wheelchair, Byrd came to the Senate and cast a vote in favor of health care reform, a cause Kennedy championed throughout his career. He proclaimed, "This is for my friend Ted Kennedy: Aye."
"He served to the end: I will never forget watching him being wheeled on to the Senate floor to cast his decisive vote for health care reform," former President Bill Clinton said in a statement today.
Stemming from his own struggles in school and college, Byrd made education a key priority in his legislative career. He established the Scholastic Recognition Award in 1969, which gave a valedictorian from every West Virginia public and private high school a special savings bond. He also helped launch the first merit-based federal scholarship program in 1985.
Byrd helped steer billions of federal dollars into economic projects into West Virginia. In the two years he served as the Democrats' majority leader, stepping down in 1989, Byrd helped send more than $1 billion in federal funds to West Virginia for highways, bridges, buildings and other facilities, some named after him.
Sen. Jay Rockefeller, also a Democratic senator from West Virginia, said it was his "greatest privilege" to serve with Byrd, and that his death "leaves a void that simply can never be filled."
"I am proud knowing that his moving life story and legacy of service and love for West Virginia will live on," Rockefeller said in a statement today.
Byrd also supported the coal industry, a leading employer in his state, a position that often put him at odds with environmentalists and other Democratic lawmakers.
Byrd was a self-professed dog lover.
"I lost one of my best friends today," he announced at a Senate Appropriations hearing in April 2002, after the death of his Maltese.
Byrd was outraged by the dogfighting charges against Atlanta Falcons quarterback Michael Vick. The senator took to the floor, delivering a scathing speech against the disgraced NFL star.