In 1951, American ex-serviceman George Whitman opened an English-language bookstore on Paris's Left Bank under the name of "Le Mistral".

[4] Much like Sylvia Beach's historic Shakespeare and Company bookstore which had closed in 1941, Whitman's store quickly became the focal point of literary culture in bohemian expatriate Paris.

[4] Other visitors were James Baldwin, Anaïs Nin, Julio Cortázar, Richard Wright, Lawrence Durrell, Max Ernst, Bertolt Brecht, William Saroyan, Terry Southern, and editors of The Paris Review, such as George Plimpton, Peter Matthiessen, and Robert Silvers.

In 1958, while dining with Whitman at a party for James Jones who had newly arrived in Paris, Beach announced that she was handing the name to him for his bookshop.

[7] In 2003, Sylvia Whitman founded FestivalandCo, a literary festival that was held biennially at the park next-door to the bookstore, Square René-Viviani.

Partnering with Bob's Bake Shop, Shakespeare and Company opened a café in 2015, located next door to the store in what had been, since 1981, an abandoned garage.

During the first lockdown in France, the bookstore was closed for two months and didn't sell online following the advice from the trade body of the Syndicat de la Librairie française.

[11] Several literary publications have had their editorial address at the bookstore, including the avant-garde journal Merlin, which is credited for having discovered Samuel Beckett, it being the first to publish him in English.

Other publications established from the bookstore include Frank magazine, edited by David Applefield with contributions from writers such as Mavis Gallant and John Berger, and Whitman's own The Paris Magazine (or "The Poor Man's Paris Review", as he called it), with contributors including Lawrence Ferlinghetti, Jean-Paul Sartre, Marguerite Duras, Pablo Neruda, and—in a more recent edition--Lucy Sante, Michel Houellebecq, and Rivka Galchen.

Other contributors to the book include Ethan Hawke, Lawrence Ferlinghetti, Allen Ginsberg, Anaïs Nin, Robert Stone, Ian Rankin, Kae Tempest, and Jim Morrison.