Gide was born in Paris on 22 November 1869, into a middle-class Protestant family. His father was a Paris University professor of law who died in 1880. His uncle was the political Economist Charles Gide. His paternal family traced its roots back to Italy, with his ancestors, the Guido's, moving to France and other western and northern European countries after converting to Protestantism during the 16th century, due to persecution.

Gide was brought up in isolated conditions in Normandy and became a prolific Writer at an early age, publishing his first novel, The Notebooks of André Walter (French: Les Cahiers d'André Walter), in 1891, at the age of twenty-one.

In 1893 and 1894, Gide travelled in Northern Africa, and it was there that he came to accept his attraction to boys.

In 1895, after his mother's death, he married his cousin Madeleine Rondeaux, but the marriage remained unconsummated. In 1896, he became mayor of La Roque-Baignard, a commune in Normandy.

In 1901, Gide rented the property Maderia in St. Brélade's Bay and lived there while residing in Jersey. This period, 1901–07, is commonly seen as a time of apathy and turmoil for him.

In 1908, Gide helped found the literary magazine Nouvelle Revue Française (The New French Review). In 1916, Marc Allégret, only 15 years old, became his lover. Marc was the son – one of five children – of Elie Allégret, who years before had been hired by Gide's mother to tutor her son in light of his weak grades in school, after which he and Gide became fast friends; Allégret was best man at Gide's wedding. Gide and Marc fled to London, in retribution for which his wife burned all his correspondence – "the best part of myself," he later commented. In 1918, he met Dorothy Bussy, who was his friend for over thirty years and translated many of his works into English.

In the 1920s, Gide became an inspiration for Writers such as Albert Camus and Jean-Paul Sartre. In 1923, he published a book on Fyodor Dostoyevsky; however, when he defended homosexuality in the public edition of Corydon (1924) he received widespread condemnation. He later considered this his most important work.

In 1923, he sired a daughter, Catherine, by Elisabeth van Rysselberghe, a woman who was much younger than he. He had known her for a long time, as she was the daughter of his closest female friend, Maria Monnom, the wife of his friend the Belgian neo-impressionist Painter Théo van Rysselberghe. This caused the only crisis in the long-standing relationship between Allégret and Gide and damaged the relation with van Rysselberghe. This was possibly Gide's only sexual liaison with a woman, and it was brief in the extreme. Catherine became his only descendant by blood. He liked to call Elisabeth "La Dame Blanche" ("The White Lady"). Elisabeth eventually left her husband to move to Paris and manage the practical aspects of Gide's life (they had adjoining apartments built for each on the rue Vavin). She worshiped him, but evidently they no longer had a sexual relationship. Gide's legal wife, Madeleine, died in 1938. Later he explored their unconsummated marriage in his memoir of Madeleine, Et Nunc Manet in Te.

In 1924, he published an autobiography, If it Die... (French: Si le grain ne meurt).

After 1925, he began to campaign for more humane conditions for convicted Criminals.

From July 1926 to May 1927, he travelled through the French Equatorial Africa colony with his lover Marc Allégret. Gide went successively to Middle Congo (now the Republic of the Congo), Ubangi-Shari (now the Central African Republic), briefly to Chad and then to Cameroon before returning to France. He related his peregrinations in a journal called Travels in the Congo (French: Voyage au Congo) and Return from Chad (French: Retour du Tchad). In this published journal, he criticized the behavior of French Business interests in the Congo and inspired reform. In particular, he strongly criticized the Large Concessions regime (French: régime des Grandes Concessions), i.e., a regime according to which part of the colony was conceded to French companies and where these companies could exploit all of the area's natural resources, in particular rubber. He related, for instance, how natives were forced to leave their village for several weeks to collect rubber in the forest, and went as far as comparing their exploitation to slavery. The book had important influence on anti-colonialism movements in France and helped re-evaluate the impact of colonialism.

"Each volume that Gide wrote was intended to challenge itself, what had preceded it, and what could conceivably follow it. This characteristic, according to Daniel Moutote in his Cahiers de André Gide essay, is what makes Gide's work 'essentially modern': the 'perpetual renewal of the values by which one lives.'" Gide wrote in his Journal in 1930: "The only drama that really interests me and that I should always be willing to depict anew, is the debate of the individual with whatever keeps him from being authentic, with whatever is opposed to his integrity, to his integration. Most often the obstacle is within him. And all the rest is merely accidental."

Known for his fiction as well as his autobiographical works, Gide exposes to public view the conflict and eventual reconciliation of the two sides of his personality, split apart by a straitlaced traducing of education and a narrow social moralism. Gide's work can be seen as an investigation of freedom and empowerment in the face of moralistic and puritanical constraints, and centres on his continuous effort to achieve intellectual honesty. His self-exploratory texts reflect his search of how to be fully oneself, including owning one's sexual nature, without at the same time betraying one's values. His political activity is informed by the same ethos, as indicated by his repudiation of communism after his 1936 voyage to the USSR.

In 1939, Gide became the first living author to be published in the prestigious Bibliothèque de la Pléiade.

Gide's surviving letters run into the thousands. But it is the Journal that Sheridan calls "the pre-eminently Gidean mode of expression." "His first novel emerged from Gide's own journal, and many of the first-person narratives read more or less like journals. In Les faux-monnayeurs, Edouard's journal provides an alternative voice to the narrator's." "In 1946, when Pierre Herbert asked Gide which of his books he would choose if only one were to survive," Gide replied, 'I think it would be my Journal.'" Beginning at the age of eighteen or nineteen, Gide kept a journal all of his life and when these were first made available to the public, they ran to thirteen hundred pages.

He left France for Africa in 1942 and lived in Tunis until the end of World War II. In 1947, he received the Nobel Prize in Literature. He devoted much of his last years to publishing his Journal. Gide died in Paris on 19 February 1951. The Roman Catholic Church placed his works on the Index of Forbidden Books in 1952.

André Gide's writings spanned many genres – "As a master of prose narrative, occasional dramatist and translator, literary critic, letter Writer, Essayist, and diarist, André Gide provided twentieth-century French literature with one of its most intriguing examples of the man of letters."

As a whole, "The works of André Gide reveal his passionate revolt against the restraints and conventions inherited from 19th-century France. He sought to uncover the authentic self beneath its contradictory masks."