Varian Fry was educated at Hotchkiss and Taft School and Harvard University. He founded Hound & Horn, an influential literary quarterly, in 1927 with Lincoln Kirstein while a Harvard undergraduate. He married Kirstein's sister, Eileen.

While working as a foreign correspondent for the American journal The Living Age, Fry visited Berlin in 1935 and personally witnessed Nazi savagery against Jews on more than one occasion and wanted to help.

Greatly disturbed by what he saw, he helped raise money to support European anti-Nazi movements. Following the occupation of France in August 1940, he went to Marseille as an agent of the newly formed Emergency Rescue Committee in an effort to help persons wishing to flee the Nazis. Fry had $3,000 and a short list of refugees under imminent threat of arrest by agents of the Gestapo. Clamoring at his door came anti-Nazi writers, avant-garde artists, musicians and hundreds of others desperately seeking any chance to escape France.

Beginning in 1940, in Marseille, despite the watchful eye of the collaborationist Vichy regime, he and a small group of volunteers hid people at the Villa Air-Bel until they could be smuggled out. More than 2,200 people were taken across the border to Spain and thence to the safety of neutral Portugal from which they made their way to the United States.

Others he helped escape on ships leaving Marseille for the French colony of Martinique, from which they too could go to the United States. Among Fry's closest associates were Americans Miriam Davenport, a former art student at the Sorbonne, and the heiress Mary Jayne Gold, a lover of the arts and the "good life" who had come to Paris in the early 1930s.

When the Nazis seized France in 1940, Gold went to Marseille, where she worked with Fry and helped finance his operation. Also working with Fry was a young academic named Albert O. Hirschman, who eventually went on to a distinguished career in America.

Especially instrumental in getting Fry the visas he needed for the artists, intellectuals and political dissidents on his list was Hiram Bingham IV, an American Vice Consul in Marseille who fought against State Department anti-Semitism and was personally responsible for issuing thousands of visas, both legal and illegal.

Among those Fry aided were:

Back home in the United States, Fry published his book in 1945 about his time in France under the title Surrender on Demand. In 1968, the US publisher Scholastic (which markets mainly to children and adolescents) published a paperback edition under the title Assignment: Rescue, and subsequent reprints have appeared under both of the above titles.

He wrote and spoke critically against U.S. immigration policies particularly relating to the issue of the fate of Jews in Europe. In a December 1942 issue of The New Republic, he wrote a scathing article titled: "The Massacre of Jews in Europe".