Ethel attended Greenwich Academy, and The Convent of the Sacred Heart in the Bronx. In September 1945, Ethel began her education at Manhattanville College of the Sacred Heart, located in Purchase, New York. It was here where she met Jean Kennedy (sister of Robert F. Kennedy); they eventually became friends and roommates.

She met Robert F. Kennedy (Bobby) during a skiing trip to Mont-Tremblant, Quebec, Canada during the winter of 1945. He was dating Ethel's sister, Patricia Skakel. Eventually that relationship ended and Ethel and Bobby started seeing each other. Ethel campaigned for John F. Kennedy in 1946, and wrote her college thesis on his book Why England Slept. Bobby and Ethel became engaged in February 1950 and married on June 17, 1950. Ethel and Bobby moved to Charlottesville, Va., where they lived while Bobby finished his last year at the University of Virginia Law School. Their first child, Kathleen, was born on July 4, 1951.

On October 4, 1955, Ethel's parents died in a plane crash when their plane ran out of fuel. Her brother George also died in a plane crash in 1966, his widow, Pat, died shortly thereafter, leaving several children.

She eventually had 11 children with Bobby; she was expecting the 11th when her husband was assassinated in 1968. Since the assassination, she has been active in preserving her husband's memory and every honor for him has been an honor for her as well.

Ethel and Bobby's children were, in chronological order: Kathleen (born 1951), Joseph (born 1952), Robert (born 1954), David (1955-1984), Courtney (born 1956), Michael (1958-1997), Kerry (born 1959), Christopher (born 1963), Matthew (born 1965), Douglas (born 1967) and Rory (born 1968).