In 1918 she married William "Lane" Rehm, a friend that she had made while at the University of Chicago. He was an artist in New York City, and she later admitted that she married him to get out of Indianapolis. The marriage lasted for only a few years and they divorced amicably in 1926. Rehm was supportive of Flanner's career until his death.
Flanner was bisexual. In 1918, the same year she married her husband, she met Solita Solano (Sarah Wilkinson). They met in Greenwich Village, and the two became lifelong lovers, although both became involved with other lovers throughout their relationship. Solita Solano was drama editor for the New York Tribune and also wrote for National Geographic. The two women are portrayed as "Nip" and "Tuck" in the 1928 novel Ladies Almanack, by Djuna Barnes, who was a friend of Flanner's. While in New York, Janet Flanner moved in the circle of the Algonquin Round Table, but was not a member. She also met the couple Jane Grant and Harold Ross through painter Neysa McMein. It was this connection that Harold Ross offered her the position of French Correspondent to the New Yorker.
After periods in Pennsylvania and New York, in her mid twenties, Flanner left the United States for Paris, quickly becoming part of the group of American writers and artists who lived in the city between World War I and World War II.
She played a crucial role in introducing her contemporaries - or at least those who read the New Yorker - to new artists in Paris, including Pablo Picasso, Georges Braque, Henri Matisse, André Gide, Jean Cocteau, and the Ballets Russes, as well as crime passionel and vernissage, the triumphant crossing of the Atlantic Ocean by Charles Lindbergh and the depravities of the Stavisky Affair.
In September 1925 Flanner published her first "Letter from Paris" in The New Yorker, launched the previous February, launching a professional association destined to last for five decades. Flanner had first came to the attention of editor Harold Ross through his first wife, Jane Grant, who was a friend of Flanner's from the Lucy Stone League, an organization that fought for women to preserve their maiden names after marriage. Flanner joined the group in 1921. Ross famously thought "Genêt" was French for "Janet".
Her prose style has since come to epitomise the "New Yorker style" - its influence can be seen decades later in the prose of Bruce Chatwin. An example: "The late Jean De Koven was an average American tourist in Paris but for two exceptions: she never set foot in the Opéra, and she was murdered."
She lived in New York City during World War II with Natalia Danesi Murray and her son William B. Murray; still writing for The New Yorker. She went back to Paris in 1944 and continued her "Letters" until finally returning to New York City in 1975 when her failing health needed extra care. In 1948 she was made a knight of Legion d'Honneur.
Her work during World War II included not only her famous "Letter from Paris" (disrupted for a period) and seminal pieces on Hitler's rise to power (1936) and the Nuremberg trials (1945), but a series of little-known weekly radio broadcasts for the NBC Blue Network during the months following the liberation of Paris in late 1944. Flanner authored one novel, The Cubical City, which achieved little success.
In 1958 she was awarded an honorary doctorate by Smith College. She covered the Suez crisis, the Soviet invasion of Hungary, and the strife in Algeria which led to the rise of Charles de Gaulle. She was a leading member of the influential coterie of mostly lesbian women that included Natalie Clifford Barney and Djuna Barnes. She was friends with Gertrude Stein and Alice B. Toklas as well as Ernest Hemingway. Flanner lived in Paris with Solano, who put away her own literary aspirations to be Flanner's personal secretary. Even though the relationship was not monogamous, they lived together for over 50 years.
Extracts of her Paris journal were turned into a piece for chorus and orchestra by composer Ned Rorem.
In 1971, she was the third guest during the infamous scuffle between Gore Vidal and Norman Mailer on the Dick Cavett Show, getting in between the two after a drunken Mailer started insulting his fellow guests and their host.
Four years later, she returned to New York City permanently to be cared for by Natalia Danesi Murray. Solano died in 1975 at the age of 87. Flanner died on 17 November, 1978 due to unknown causes.