Jacqueline married Greek shipping magnate Aristotle Onassis on the island of Skorpios. The marriage was controversial and generated considerable media attention. The marriage was largely motivated by her fear for her children's safety, as the Kennedy family was seen to be cursed.

Jacqueline spent several years traveling the world with Onassis and living a life of luxury. However, the marriage was reportedly strained by Onassis's business affairs and his relationship with Maria Callas. Onassis' children strongly disliked Jacqueline, and she was seen as an unwelcome addition to the family.

Aristotle Onassis died in Paris in 1975. Jacqueline inherited a portion of his estate after a legal battle with his daughter, Christina Onassis.