President Barack Obama praised the life of Kennedy, whose endorsement during the 2008 Democratic presidential primary helped propel the president to victory over then-rival Hillary Clinton.
"An important chapter in our history has come to an end," President Obama said in a statement Wednesday. "Our country has lost a great leader, who picked up the torch of his fallen brothers and became the greatest United States Senator of our time."
"Even as he waged a valiant struggle with a mortal illness, I've profited from his encouragement and wisdom," the president said.
President Obama's remarks on Kennedy's death:
Aides woke the president with the news of Kennedy's death shortly after 2 a.m., according to a White House spokesman. He then called the senator's widow, Victoria, around 2:25 a.m. to express his condolences.
In Washington, flags on Capitol Hill were quickly lowered to half mast as colleagues remembered the Senate's third-longest serving member.
Vice President Joe Biden credited Kennedy for bringing optimism to chamber. "It was infectious," the vice president said. "You could just see it in the nature of his debate, in the nature of his embrace, in the nature of how he every single day attacked these problems. And, you know, he was never defeatist. He never was petty -- never was petty. He was never small. And in the process of his doing, he made everybody he worked with bigger -- both his adversaries as well as his allies," the vice president recalled.
"The Kennedy family and the Senate family have together lost our patriarch," Senate Majority Leader Harry Reid, D-Nev., said in a statement. "It was a thrill of my lifetime to work with Ted Kennedy. He was a friend, the model of public service and an American icon. As we mourn his loss, we rededicate ourselves to the causes for which he so dutifully dedicated his life," Reid said.
"No one could have known the man without admiring the passion and vigor he poured into a truly momentous life," said the Senate's top Republican, Mitch McConnell of Kentucky.
Sen. Orrin Hatch, R-Utah, called Kennedy a "great elder statesman" and "treasured friend ... who lived and breathed the United States Senate and the work completed within its chamber."
Sen. Christopher J. Dodd, D-Conn., also a close Kennedy friend, said he was "not sure America has ever had a greater Senator, but I know for certain that no one has had a greater friend than I and so many others did in Ted Kennedy."
Kennedy's fellow senator from Massachusetts, John Kerry, called his longtime colleague "the best senator, the best advocate you could hope for."
Hillary Clinton, who served with Kennedy in the Senate before becoming Secretary of State, credited Kennedy for his impact on a broad array of domestic initiatives. "He was a champion for women and families, for health care, education, civil rights and the environment," Clinton said.
"We have lost Ted," she added, "but his life's work will shape our nation for years to come. His legacy will live on in the hearts and minds of millions of Americans who are freer, healthier, and more prosperous because of his efforts."
Former President Bill Clinton echoed the sentiments of his wife. "Senator Ted Kennedy was one of the most influential leaders of our time, and one of the greatest senators in American history," the former president said. "As President, I was thankful for his fierce advocacy for universal health care and his leadership in providing health coverage to millions of children. His tireless efforts have brought us to the threshold of real health care reform."
California Gov. Arnold Schwarzenegger, a Republican and husband to Kennedy's niece, Maria Shriver, remembered the senator's impact on him and his family.
"He was the rock of our family: a loving husband, father, brother and uncle. He was a man of great faith and character," Schwarzenegger said in a statement.
Nancy Reagan, wife of one of Schwarzenegger's predecessors, former President Ronald Reagan, said: "Given our political differences, people are sometimes surprised by how close Ronnie and I have been to the Kennedy family. But Ronnie and Ted could always find common ground, and they had great respect for one another. In recent years, Ted and I found our common ground in stem cell research, and I considered him an ally and a dear friend. I will miss him."
Kennedy was also remembered abroad, in Britain and Ireland in particular, for his work to promote peace in Northern Ireland. Former Prime Minister Tony Blair of Britain said he saw Kennedy's "focus and determination first hand in Northern Ireland, where his passionate commitment was matched with a practical understanding of what needed to be done to bring about peace and to sustain it. I was delighted he could join us in Belfast the day devolved government was restored. My thoughts and prayers today are with all his family and friends as they reflect on the loss of a great and good man."
The president of Ireland, Mary McAleese, said Kennedy would be remembered "as a hugely important friend to this country during the very difficult times."
Prime Minister of Australia, Kevin Rudd, "made an extraordinary contribution to American politics, an extraordinary contribution to America's role in the world."
A date has yet to be set for Kennedy's funeral, but his body will lie in repose at the John F. Kennedy Presidential Library and Museum before services at a Boston church. He will be buried at Arlington National Cemetery next to his two brothers.
President Obama, who is currently vacationing a short distance away from the Kennedy family compound on Cape Cod, is expected to deliver a eulogy.
---- Compiled from wire reports and other media sources