In September 1945, Skakel began her college education at Manhattanville College, where she was a classmate of future sister-in-law Jean Kennedy. Ethel first met Jean’s brother, Robert F. Kennedy, during a ski trip to Mont Tremblant Resort in Quebec in December 1945. During this trip, Robert Kennedy began dating Ethel’s elder sister, Patricia. After that relationship ended, he began dating Ethel. She campaigned for his elder brother, John F. Kennedy, in his 1946 campaign for the United States Congress; she also wrote her college thesis on his book Why England Slept. Skakel received a bachelor’s degree from Manhattanville in 1949.

Robert Kennedy and Ethel Skakel became engaged in February 1950 and were married on June 17, 1950, at St. Mary’s Catholic Church in Greenwich, Connecticut.

Ethel Skakel was born in Chicago, to businessman George Skakel and secretary Ann Brannack. Her parents were killed in a 1955 plane crash. She was the Skakels’ third of four daughters and sixth child of seven, having five older siblings, Georgeann, James, George Jr., Rushton, and Patricia, and one younger sister, Ann. George was a Protestant of Dutch descent while Ann was a Catholic of Irish ancestry. Ethel and her siblings were raised Catholic in Greenwich, Connecticut. George Skakel was the founder of Great Lakes Carbon Corporation, now a division of SGLCarbon. She attended the all-girls Greenwich Academy in Greenwich and graduated from the Convent of the Sacred Heart in Manhattan in 1945.

In 1962, President Kennedy assigned Ethel and Robert to tour fourteen countries within a 28-day goodwill trip. Though the trip was said to be informal, the host countries viewed her and Robert as stand-ins for the President and First Lady.

On November 22, 1963, Ethel learned of President Kennedy’s assassination from her husband. She had answered the phone, identified the caller as J. Edgar Hoover and handed the phone over to Robert, who then informed her of the shooting. The FBI Director had never called the Attorney General’s home before. Ethel was reportedly devastated by the assassination and worried for President Kennedy’s children.

Shortly after midnight on June 5, 1968, Robert F. Kennedy was mortally wounded by Sirhan Sirhan and died early the next day. U.S. President Lyndon B. Johnson declared a national day of mourning. Ethel sent Johnson a handwritten note on June 19, thanking him and his wife, First Lady Lady Bird Johnson, for the help they had given her and the Kennedy family. Following her husband’s assassination, Ethel Kennedy publicly stated that she would never marry again. For a time, she was escorted to dinners, parties, and the theater by singer and family friend Andy Williams.

Ethel Kennedy founded the Robert F. Kennedy Center for Justice and Human Rights (now known as Robert F. Kennedy Human Rights in 1968.

In 1981, President Ronald Reagan honored Kennedy with the Robert F. Kennedy medal in the White House Rose Garden.

In the media, Ethel Kennedy’s parenting has been alternately described as “quaint”, “questionable”, “tough love”, “inattentive”, and “angry”. In a 1997 piece on the Kennedys’ children, Vanity Fair noted “one son’s death by drug overdose, another’s arrest for heroin possession, and the involvement of Joe himself in reckless driving that left a girl paralyzed for life, along with a general trend of overindulgence among the sons that has sent several of them into rehab”. These remarks respectively referred to her sons David, Robert Jr., and Joseph.

In February 2001, Kennedy visited Rodolfo Montiel and another peasant activist at their jail in Iguala, presenting Rodolfo with the Chico Mendes Award on behalf of American environmental group, the Sierra Club.

During the 2008 Democratic Party presidential primaries, Ethel Kennedy endorsed Barack Obama. She publicly supported and held fundraisers at Hickory Hill for numerous politicians that included Virginia gubernatorial candidate Brian Moran. Kennedy hosted a $6-million fundraising dinner for Obama at Hickory Hill in June 2008. The $28,500-a-plate dinner was headlined by former Democratic presidential candidate and DNC chairman Howard Dean.

Kennedy sold Hickory Hill for $8.25 million in December 2009.

In 2012, Kennedy appeared in a documentary about her life; the documentary was directed by her youngest child, daughter Rory. The documentary, entitled Ethel, covers Kennedy’s early political involvement, her life with Robert F. Kennedy, and the years following his death when she raised eleven children on her own. It features interviews with Ethel and her children interspersed with family videos and archival photos.

In August 2014, Kennedy nominated President Barack Obama to do the Ice Bucket Challenge as part of an effort to raise funds and awareness about amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease). Obama declined to perform the fundraising stunt, but expressed appreciation to Kennedy and made a monetary donation to the cause.

As of 2014, Kennedy reportedly wintered in Florida and summered in Cape Cod, Massachusetts. Five years later, she was known to reside at the Kennedy Compound in Hyannis Port, Massachusetts.

In 2014, a bridge over the Anacostia River was renamed the Ethel Kennedy Bridge in her honor, in recognition of her advocacy for environmentalism and social causes in the District of Columbia.

Also in 2014, she was awarded the Presidential Medal of Freedom by President Obama for her dedication to “advancing the cause of social justice, human rights, environmental protection, and poverty reduction by creating countless ripples of hope to effect change around the world.”

In March 2016, Kennedy was among hundreds who marched near the home of Wendy’s chairman Nelson Peltz in Palm Beach, Florida, as part of an effort by the Coalition of Immokalee Workers, a farm workers’ group, to convince the company to pay an additional one cent per pound of tomatoes to increase the wages of field workers.