But the senator also navigated a rocky, painful and some say cursed, road as part of the Kennedy clan. The family has confronted monumental challenges -- including assassinations, deadly plane and car accidents, public failings, family difficulties, legislative hurdles, and most recently Ted Kennedy's devastating, terminal illness.
Through those rough waters, Ted Kennedy continued to sail on.
"The phrase that he's used with me over the years is 'Keep on keeping on,'" Boston Globe columnist Thomas Oliphant said in an interview with ABC News. "You can't puzzle through something as enormous and almost unspeakable as these tragedies are. But you can get up tomorrow and do something."
Kennedy's long battle with brain cancer was the last struggle of many during his 77 years, but the senator learned about death early on.
Born Feb. 22, 1932, as the youngest of eight, Kennedy was just 12 years old when his oldest brother, Joseph, Jr., a navy flier in World War II, was shot down during a secret bombing run in 1944. Nearly four years later in 1948, his second-oldest sister, Kathleen, died in a plane crash during a trip to the South of France at the age of 28.
View the Kennedy family tree.
Visit ABC News' special section on Ted Kennedy.
Watch video of historic Kennedy moments.
See photos of Sen. Ted Kennedy's life.
See photos of the Kennedy family's history of privilege and loss.
Kennedy faced ups and downs as a young adult before beginning a career in politics. After graduating from Milton Academy, Kennedy enrolled at Harvard University in 1950, but was expelled for having another student take his Spanish final exam.
He then enlisted for two years in the U.S. Army, and worked at the Supreme Headquarters Allied Powers in Paris before returning to Harvard in 1956 to obtain his degree.
Kennedy then enrolled in law school at the University of Virginia, receiving his law degree in 1959. He married his first wife, Virginia Joan Bennett in 1958, with whom he had three children, Kara Anne, Edward M., Jr., and Patrick Joseph. While still in law school, Kennedy began to build his political credentials by managing his brother John F. Kennedy's 1958 Senate re-election campaign. In 1960, he served as Western states coordinator for his brother's successful democratic presidential campaign.
After his brother's victory in 1960, Kennedy went on to take a dollar-a-year job as assistant to the Suffolk County, Mass., district attorney. He won his brother's former seat in the Senate in 1962, at just 30 years old.
Tragedy struck a year later, in 1963, when his second-oldest brother, President John F. Kennedy, was assassinated.
A year later, as he was running for re-election to a full-Senate term, Ted Kennedy broke his back in the June 1964 plane crash that killed his aide, Edward Moss. The injury incapacitated him throughout the campaign. Despite his injury, he won the election with 74.4 percent of the vote.
Four years later, in 1968, his third-oldest and only surviving brother, N.Y. Sen. Robert Kennedy, was assassinated while campaigning for the presidency.
Ted Kennedy went into a period of withdrawal, resisting efforts to draft him for the 1968 presidential democratic nomination.