Following the assassination of Bobby Kennedy, Jackie defies public opinion and marries Greek shipping magnate Aristotle Onassis. Ted Kennedy is pressured to replace his fallen brother and continue the legacy of "Camelot" by running for the White House himself.

The Kennedy family is shaken to its core when Ted's car accident at Chappaquiddick results in the death of his female companion. Jackie returns from Greece - over the objections of Onassis - to help the Kennedys, only to find herself drawn into their attempt to save Ted's career by evading justice.

The Chappaquiddick disaster is resolved, though a permanent cloud hangs over Ted's public life and his conscience. Jackie's marriage to Onassis ends when the death of his son convinces him that she's the bearer of the "Kennedy curse". She returns with her children to live in New York, but her relationship with JFK Jr is strained as he chafes under the burden of his father's name. Ted falls deeper into alcoholism and depression when his son suffers a catastrophic illness.

By August of 1961 the Russians move troops into Berlin, though their intentions are unclear. JFK prepares for the possibility that Khrushchev may try to take the city. Bobby announces the formation of the Organized Crime Division. Chicago mobster Sam Giancana is livid about it, and blames Frank Sinatra, who had arranged a meeting between the gangster and Joe Kennedy Sr before the 1960 election.

At home and with little to do, for the first time in his life Joe Sr feels useless. Rose is angry and feels her sons have abandoned their father. Then, terrible news: Joe suffers a stroke from which he may never fully recover. In the South, civil rights demonstrators are protesting. James Meredith, a black student, is attempting to gain admission to the University of Mississippi and riots are imminent.

Jack and Bobby try to convince their father that Bobby's being named Attorney General would be a major mistake. Quickly drawn into the Bay of Pigs crisis, virtually all of Jack's advisers - military and civilian - urge him to go ahead with the invasion. JFK is unsure that the plan will work, and he worries that the operation will be linked back to the US - causing major problems with Cuba's ally, the Soviet Union.