Kennedy pleaded guilty to a misdemeanor charge of leaving the scene of an accident. He received a two-month suspended sentence and lost his driver's license for a year, but the political price was higher.
Kennedy was re-elected to the Senate in 1970, but the accident at Chappaquiddick effectively squashed his presidential hopes.
He ran unsuccessfully for the Democratic nomination in 1979 against incumbent President Jimmy Carter.
Once when his daughter Kara, then 19, was passing out campaign leaflets, a man took one and said to her, "You know your father killed a young woman about your age, don't you?"
Sen. Ted Kennedy was not done confronting personal tragedy.
In 1973, 12-year-old Teddy Jr. was diagnosed with bone cancer, and he had to have a leg amputated. Kennedy's marriage to Joan deteriorated. Some blamed her drinking, others cited his alleged womanizing. The couple divorced in 1981.
In contrast, Kennedy's career in the Senate continued to flourish.
He supported teachers' unions, women's and abortion rights, and health care reform. He sponsored the Family and Medical Leave Act. And he was seen as a stalwart of the Democratic Party, delivering several rousing speeches at conventions.
Former Boston Glober reporter Tom Oliphant, who covered Kennedy's career in Washington, observed, "It's not all back slapping and, and personal relationships. I think one of the things that sets Kennedy's politics apart is his, what I call his dirty little secret. He works like a dog."
Political analyst Mark Shields said Kennedy's "concerns were national concerns, but his forum for achieving his ends and changing policy, became the Senate. And he mastered it like nobody else I've ever seen."
But another family incident exposed Kennedy's vulnerabilities and held him up to public censure.
A nephew, William Kennedy Smith, was accused of raping a woman at the family's estate in Palm Beach, Fla. The case generated lurid headlines around the world. Kennedy was at the estate at the time of the alleged attack and had been at the bar where Smith met his accuser.
Eyebrows were raised even further when a young woman who had been with Kennedy's son Patrick that night revealed that she had seen the senator roaming around the house at night, wearing an oxford shirt but no trousers.
Smith was acquitted following a highly sensational trial, but the incident definitely left a dent in Kennedy's armor. His alleged heavy drinking and womanizing were widely lampooned, and in October 1991 he thought it prudent to be low-key in his opposition to Supreme Court nominee Clarence Thomas, who had been accused of sexually harassing a former subordinate.
Kennedy's life, both professional and personal, took a turn for the better in 1992.
He married Victoria Reggie, a divorced attorney with two children from a previous marriage, Curran and Caroline. That year Kennedy also supported Bill Clinton, an open admirer of the Kennedy clan.
"Well, sometime during our courtship, I realized that I didn't want to live the rest of my life without Vicki," Kennedy said about his wife of nearly 30 years. "And since we have been together, it's made my life a lot more fulfilling. I think more serene, kind of emotional stability."