Henry Graham Greene was born in 1904 in St. John’s House, a boarding house of Berkhamsted School, Hertfordshire, where his father was housemaster. He was the fourth of six children; his younger brother, Hugh, became Director-General of the BBC, and his elder brother, Raymond, an eminent physician and mountaineer.

In 1910 Charles Greene succeeded Dr Fry as headmaster of Berkhamsted. Graham also attended the school as a boarder. Bullied and profoundly depressed, he made several suicide attempts, including, as he wrote in his autobiography, by Russian roulette and by taking aspirin before going swimming in the school pool. In 1920, aged 16, in what was a radical step for the time, he was sent for psychoanalysis for six months in London, afterwards returning to school as a day student. School friends included Claud Cockburn the Journalist, and Peter Quennell the Historian.

In 1922, Greene was for a short time a member of the Communist Party of Great Britain, and sought an invitation to the new Soviet Union, of which nothing came. In 1925, while he was an undergraduate at Balliol College, Oxford, his first work, a poorly received volume of poetry titled Babbling April, was published.

Greene suffered from periodic bouts of depression while at Oxford, and largely kept to himself. Of Greene's time at Oxford, his contemporary Evelyn Waugh noted that: "Graham Greene looked down on us (and perhaps all undergraduates) as childish and ostentatious. He certainly shared in none of our revelry." He graduated in 1925 with a second-class degree in history.

After meeting his Future wife Vivien Dayrell-Browning, Greene was baptised into the Catholic faith on 26 February 1926, and they were married on 15 October 1927 at St Mary's Church, Hampstead, North London. The Greenes had two children, Lucy Caroline (born 1933) and Francis (born 1936).

Greene's first published novel was The Man Within (1929). Favourable reception emboldened him to quit his sub-editor job at The Times and work as a full-time Novelist. The next two books, The Name of Action (1930) and Rumour at Nightfall (1932), were unsuccessful; and he later disowned them. His first true success was Stamboul Train (1932) which was taken on by the Book Society and adapted as the film Orient Express, in 1934.

Greene was one of the most "cinematic" of twentieth-century writers; most of his novels and many of his plays and short stories have been adapted for film or television. The Internet Movie Database lists 66 titles between 1934 and 2010 based on Greene material. Some novels were filmed more than once, such as Brighton Rock in 1947 and 2011, The End of the Affair in 1955 and 1999, and The Quiet American in 1958 and 2002. The 1936 thriller A Gun for Sale was filmed at least five times under different titles. Greene received an Academy Award nomination for the screenplay for the 1948 Carol Reed film The Fallen Idol, adapted from his own short story The Basement Room. He also wrote several original screenplays. In 1949, after writing the novella as "raw material", he wrote the screenplay for a classic film noir, The Third Man, also directed by Carol Reed, and featuring Orson Welles. In 1983 The Honorary Consul, published ten years earlier, was released as a film under its original title, starring Michael Caine and Richard Gere. Author and Screenwriter Michael Korda contributed a foreword and introduction to this novel in a commemorative edition.

Greene first left Europe at 30 years of age in 1935 on a trip to Liberia that produced the travel book Journey Without Maps. His 1938 trip to Mexico to see the effects of the government's campaign of forced anti-Catholic secularisation was paid for by the publishing company Longman, thanks to his friendship with Tom Burns. That voyage produced two books, the factual The Lawless Roads (published as Another Mexico in the U.S.) and the novel The Power and the Glory. In 1953 the Holy Office informed Greene that The Power and the Glory was damaging to the reputation of the priesthood; but later, in a private audience with Greene, Pope Paul VI told him that, although parts of his novels would offend some Catholics, he should ignore the criticism.

He supplemented his novelist's income with freelance journalism, book and film reviews for The Spectator, and co-editing the magazine Night and Day. Greene's 1937 film review of Wee Willie Winkie, for Night and Day – which said that the nine-year-old star, Shirley Temple, displayed "a dubious coquetry" which appealed to "middle-aged men and clergymen" – provoked Twentieth Century Fox successfully to sue for £3,500 plus costs, which resulted in the magazine folding, and Greene leaving the UK to live in Mexico until after the trial was over. While in Mexico, Greene developed the ideas for the novel often considered his masterpiece, The Power and the Glory.

Catholicism's prominence decreased in his later writings. According to Ernest Mandel in his Delightful Murder: a Social History of the Crime Story: "Greene started out as a conservative agent of the British intelligence services, upholding such reactionary causes as the struggle of the Catholic Church against the Mexican revolution (The Power and the Glory, 1940), and arguing the necessary merciful function of religion in a context of human misery (Brighton Rock, 1938; The Heart of the Matter, 1948). The better he came to know the socio-political realities of the third world where he was operating, and the more directly he came to be confronted by the rising tide of revolution in those countries, the more his doubts regarding the imperialist cause grew, and the more his novels shifted away from any identification with the latter." The supernatural realities that haunted the earlier work declined and were replaced by a humanistic perspective, a change reflected in his public criticism of orthodox Catholic teaching.

Greene collected several literary awards for his novels, including the 1941 Hawthornden Prize for The Power and the Glory and the 1948 James Tait Black Memorial Prize for The Heart of the Matter. As an author, he received the 1968 Shakespeare Prize and the 1981 Jerusalem Prize, a biennial literary award given to Writers whose works have dealt with themes of human freedom in society. In 1986, he was awarded Britain's Order of Merit.

Greene is regarded as a major 20th century Novelist, and was described by John Irving, prior to Greene's death, as "the most accomplished living Novelist in the English language." He had acquired a reputation by 1943 of being the "leading English male Novelist of his generation", and at the time of his death in 1991 had a reputation as a Writer of both deeply serious novels on the theme of Catholicism, and of "suspense-filled stories of detection". Acclaimed during his lifetime, he was shortlisted in 1966 for the Nobel Prize for Literature. In 1967, Greene was among the final three choices, according to Nobel records unsealed on the 50th anniversary in 2017. The committee also considered Jorge Luis Borges and Miguel Ángel Asturias, with the latter the chosen winner.

Beginning in 1946, Greene had an affair with Catherine Walston, the wife of Harry Walston, a wealthy farmer and Future life peer. That relationship is generally thought to have informed the writing of The End of the Affair, published in 1951, when the affair came to an end. Greene had left his family in 1947, but in accordance with Catholic teaching, Vivien refused to grant him a divorce, and they remained married until Greene's death in 1991.

In 1949, when the New Statesman held a contest for parodies of Greene's writing style, he submitted an entry under the name "N. Wilkinson" and won second prize. His entry comprised the first two paragraphs of a novel, apparently set in Italy, The Stranger's Hand: An Entertainment. Greene's friend Mario Soldati, a Piedmontese Novelist and film Director, believed it had the makings of a suspense film about Yugoslav spies in postwar Venice. Upon Soldati's prompting, Greene continued writing the story as the basis for a film script. Apparently he lost interest in the project, leaving it as a substantial fragment that was published posthumously in The Graham Greene Film Reader (1993) and No Man's Land (2005). A script for The Stranger's Hand was written by Guy Elmes on the basis of Greene's unfinished story, and filmed by Soldati in 1954. In 1965 Greene again entered a similar New Statesman competition pseudonymously, and won an honourable mention.

By the 1950s Graham Green was generally acknowledged as one of the finest Writers of his generation.

Greene also wrote short stories and plays, which were well received, although he was always first and foremost a Novelist. His first play, The Living Room, debuted in 1953.

Greene first travelled to Haiti in 1954, where The Comedians (1966) is set, which was then under the rule of dictator François Duvalier, known as "Papa Doc", frequently staying at the Hotel Oloffson in Port-au-Prince. And, in the late 1950s, as inspiration for his novel, A Burnt-Out Case (1960), Greene spent time travelling around Africa visiting a number of leper colonies in the Congo Basin and in what were then the British Cameroons. During this trip in late February and early March 1959, he met several times with Andrée de Jongh a Belgian resistance fighter responsible for establishing an escape route for downed airmen from Belgium to the Pyrenees

In 1957, just months after Fidel Castro had begun his revolutionary final assault on the Batista regime in Cuba, Greene played a small role in helping the Revolutionaries, as a secret courier transporting warm clothing for Castro's rebels hiding in the hills during the Cuban winter. Greene was said to have a fascination with strong Leaders, which may have accounted for his interest in Castro, whom he later met. After one visit Castro gave Greene a painting he had done, which hung in the living room of the French house where the author spent the last years of his life. Greene did later voice doubts about Castro's Cuba, telling a French interviewer in 1983, "I admire him for his courage and his efficiency, but I question his authoritarianism," adding: "All successful revolutions, however idealistic, probably betray themselves in time."

As his career lengthened, both Greene and his readers found the distinction between entertainments and novels increasingly problematic. The last book Greene termed an entertainment was Our Man in Havana in 1958. When Travels with My Aunt was published eleven years later, many reviewers noted that Greene had designated it a novel, even though, as a work decidedly comic in tone, it appeared closer to his last two entertainments, Loser Takes All and Our Man in Havana, than to any of the novels. Greene, they speculated, seemed to have dropped the category of entertainment. This was soon confirmed. In the Collected Edition of Greene's works published in 22 volumes between 1970 and 1982, the distinction between novels and entertainments is no longer maintained. All are novels.

After falling victim to a financial swindler, Greene chose to leave Britain in 1966, moving to Antibes, to be close to Yvonne Cloetta, whom he had known since 1959, a relationship that endured until his death. In 1973 he had an uncredited cameo appearance as an insurance company representative in François Truffaut's film Day for Night. In 1981 Greene was awarded the Jerusalem Prize, awarded to Writers concerned with the freedom of the individual in society.

Throughout his life, Greene travelled far from England, to what he called the world's wild and remote places. The travels led to his being recruited into MI6 by his sister, Elisabeth, who worked for the agency. Accordingly, he was posted to Sierra Leone during the Second World War. Kim Philby, who would later be revealed as a Soviet agent, was Greene's supervisor and friend at MI6. Greene later wrote an introduction to Philby's 1968 memoir, My Silent War. As a Novelist Greene wove the characters he met and the places where he lived into the fabric of his novels.

He lived the last years of his life in Vevey, on Lake Geneva in Switzerland, the same town Charlie Chaplin was living in at this time. He visited Chaplin often, and the two were good friends. His book Doctor Fischer of Geneva or the Bomb Party (1980) bases its themes on combined philosophic and geographic influences. He had ceased going to mass and confession in the 1950s, but in his final years began to receive the sacraments again from Father Leopoldo Durán, a Spanish priest, who became a friend.

In 1984, in celebration of his 80th birthday, the brewery Greene's great-grandfather had founded in 1799 made a special edition of its 'St. Edmunds' ale for him, with a special label in his honour. Commenting on turning 80, Greene said, "The big advantage...is that at 80 you are more likely these days to beat out encountering your end in a nuclear war", adding, "the other side of the Problem is that I really don't want to survive myself [which] has nothing to do with nukes, but with the body hanging around while the mind departs."

In 1986 Greene was awarded Britain's Order of Merit. He died in 1991 at age 86 of leukaemia and was buried in Corseaux cemetery.

Greene had a history of depression, which had a profound effect on his writing and personal life. In a letter to his wife, Vivien, he told her that he had "a character profoundly antagonistic to ordinary domestic life," and that "unfortunately, the disease is also one's material." william Golding described Greene as "the ultimate chronicler of twentieth-century man's consciousness and anxiety." He died in 1991, at age 86, of leukaemia, and was buried in Corseaux cemetery.

His short story "The Destructors" was featured in the 2001 film Donnie Darko.

In 2009 The Strand Magazine began to publish in serial form a newly discovered Greene novel titled The Empty Chair. The manuscript was written in longhand when Greene was 22 and newly converted to Catholicism.

He is the subject of the 2013 documentary film, Dangerous Edge: A Life of Graham Greene.

Michael Korda a lifelong friend of Greene and later his Editor at Simon & Schuster once observed Greene at work. Korda observed that Greene wrote in a small black leather notebook with a black fountain pen and would write approximately 500 words. Once he reached 500 he would put his pen away and be done for the day. Korda described this as Graham's daily penance—once he finished he put the notebook away for the rest of the day.