Malraux was born in Paris in 1901, the son of Fernand-Georges Malraux and Berthe Lamy (Malraux). His parents separated in 1905 and eventually divorced. There are suggestions that Malraux's paternal grandfather committed suicide in 1909.

The British Colonel T. E. Lawrence, aka "Lawrence of Arabia", holds a sinister reputation in France as the man who was supposedly responsible for France's troubles in Syria in the 1920s. An exception was Malraux who regarded Lawrence as a role model, the intellectual-cum-man of action and the romantic, enigmatic hero. Malraux often admitted to having a "certain fascination" with Lawrence, and it has been suggested that Malraux's sudden decision to abandon the Surrealist literary scene in Paris for adventure in the Far East was prompted by a Desire to emulate Lawrence who began his career as an archaeologist in the Ottoman Empire excavating the ruins of the ancient city of Carchemish in the vilayet of Aleppo in what is now modern Syria. As Lawrence had first made his reputation in the Near East digging up the ruins of an ancient civilization, it was only natural that Malraux should go to the Far East to likewise make his reputation in Asia digging up ancient ruins. Lawrence considered himself a Writer first and foremost while also presenting himself as a man of action, the Nietzschean hero who triumphs over both the environment and men through the force of his will, a persona that Malraux consciously imitated. Malraux often wrote about Lawrence, whom he described admiringly as a man with a need for "the absolute", for whom no compromises were possible and for whom going all the way was the only way. Along the same lines, Malraux argued that Lawrence should not be remembered mainly as a guerrilla leader in the Arab Revolt and the British liaison officer with the Emir Faisal, but rather as a romantic, lyrical Writer as writing was Lawrence's first passion, which also described Malraux very well. Although Malraux courted fame through his novels, poems and essays on art in combination with his adventures and political activism, he was an intensely shy and private man who kept to himself, maintaining a distance between himself and others. Malraux's reticence led his first wife Clara to later say she barely knew him during their marriage.

In 1923, aged 22, Malraux and Clara left for the French Protectorate of Cambodia. Angkor Wat is a huge 12th century Hindu temple situated in the old capital of the Khmer empire. Angkor (Yasodharapura) was "the world’s largest urban settlement" in the 11th and 12th centuries supported by an elaborate network of canals and roads across mainland Southeast Asia before decaying and falling into the jungle. The rediscovery of the ruins of Angkor Wat (the Khmers had never fully abandoned the temples of Angkor) in the jungle by the French Explorer Henri Mouhot in 1861 had given Cambodia a romantic reputation in France, as the home of the vast, mysterious ruins of the Khmer empire. Upon reaching Cambodia, Malraux, Clara and friend Louis Chevasson undertook an expedition into unexplored areas of the former imperial settlements in search of hidden temples, hoping to find artifacts and items that could be sold to art Collectors and museums. At about the same time archaeologists, with the approval of the French government, were removing large numbers of items from Angkor - many of which are now housed in the Guimet Museum in Paris. On his return, Malraux was arrested and charged by French colonial authorities for removing a bas-relief from the exquisite Banteay Srei temple. Malraux, who believed he had acted within the law as it then stood, contested the charges but was unsuccessful.

Malraux's experiences in Indochina led him to become highly critical of the French colonial authorities there. In 1925, with Paul Monin, a progressive Lawyer, he helped to organize the Young Annam League and founded a newspaper L'Indochine to champion Vietnamese independence. After falling afoul of the French authorities, Malraux claimed to have crossed over to China where he was involved with the Kuomintang and their then allies, the Chinese Communists in their struggle against the Warlords in the Great Northern Expedition before they turned on each other in 1927, which marked the beginning of the Chinese Civil War that was to last on and off until 1949. In fact, Malraux did not first visit China until 1931 and he did not see the bloody suppression of the Chinese Communists by the Kuomintang in 1927 first-hand as he often implied that he did, although he did do much reading on the subject.

On his return to France, Malraux published The Temptation of the West (1926). The work was in the form of an exchange of letters between a Westerner and an Asian, comparing aspects of the two cultures. This was followed by his first novel The Conquerors (1928), and then by The Royal Way (1930) which reflected some of his Cambodian experiences. The American literary critic Dennis Roak described Les Conquérants as influenced by The Seven Pillars of Wisdom as it was narrated in the present tense "...with its staccato snatches of dialogue and the images of sound and sight, light and darkness, which create a compellingly haunting atmosphere." Les Conquérants was set in the summer of 1925 against the backdrop of the general strike called by the Chinese Communist Party (CCP) and Kuomintang in Hong Kong and Canton, the novel concerns political intrigue amongst the "anti-imperialist" camp. The novel is narrated by an unnamed Frenchman who travels from Saigon to Hong Kong to Canton to meet an old friend named Garine who is a professional revolutionary working with Mikhail Borodin, who in real life was the Comintern's principle agent in China. The Kuomintang are depicted rather unflatteringly as conservative Chinese nationalists uninterested in social reform, another faction is led by Hong, a Chinese Assassin committed to revolutionary violence for the sake of violence, and only the Communists are portrayed relatively favorably. Much of the dramatic tension between the novel concerns a three-way struggle between the hero, Garine and Borodin who is only interested in using the revolution in China to achieve Soviet foreign policy goals. The fact that the European characters are considerably better drawn than the Asian characters reflected Malraux's understanding of China at the time more of an exotic place where Europeans played out their own dramas rather than a place to be understood in its own right. Initially, Malraux's writings on Asia reflected the influence of "Orientalism" presenting the Far East as strange, exotic, decadent, mysterious, sensuous and violent, but Malraux's picture of China grew somewhat more humanized and understanding as Malraux disregarded his Orientalist and Eurocentric viewpoint in favor of one that presented the Chinese as fellow human beings.

During the 1930s, Malraux was active in the anti-fascist Popular Front in France. At the beginning of the Spanish Civil War he joined the Republican forces in Spain, serving in and helping to organize the small Spanish Republican Air Force. Curtis Cate, one of his biographers, claims that Malraux was slightly wounded twice during efforts to stop the Battle of Madrid in 1936 as the Spanish Nationalists attempted to take Madrid, but the Historian Hugh Thomas claims otherwise.

In 1933 Malraux published Man's Fate (La Condition Humaine), a novel about the 1927 failed Communist rebellion in Shanghai. Despite Malraux's attempts to present his Chinese characters as more three dimensional and developed than he did in Les Conquérants , his biographer Oliver Todd wrote he could not "quite break clear of a conventional idea of China with coolies, bamboo shoots, opium smokers, destitutes, and prostitutes", which were the standard French stereotypes of China at the time. The work was awarded the 1933 Prix Goncourt. After the breakdown of his marriage with Clara, Malraux lived with Journalist and Novelist Josette Clotis, starting in 1933. Malraux and Josette had two sons: Pierre-Gauthier (1940–1961) and Vincent (1943–1961). During 1944, while Malraux was fighting in Alsace, Josette died, aged 34, when she slipped while boarding a train. His two sons died together in 1961 in an automobile accident.

On 22 February 1934, Malraux together with Édouard Corniglion-Molinier embarked on a much publicized expedition to find the lost capital of the Queen of Sheba mentioned in the Old Testament. Saudi Arabia and Yemen were both remote, dangerous places that few Westerners visited at the time, and what made the expedition especially dangerous was while Malraux was searching for the lost cities of Sheba, King Ibn Saud of Saudi Arabia invaded Yemen, and the ensuring Saudi-Yemeni war greatly complicated Malraux's search. After several weeks of flying over the deserts in Saudi Arabia and Yemen, Malraux returned to France to announce that ruins he found up in the mountains of Yemen were the capital of the Queen of Sheba. Through Malraux's claim is not generally accepted by archeologists, the expedition bolstered Malraux's fame and provided the material for several of his later essays.

The French government sent aircraft to Republican forces in Spain, but they were obsolete by the standards of 1936. They were mainly Potez 540 bombers and Dewoitine D.372 fighters. The slow Potez 540 rarely survived three months of air missions, flying at 160 knots against enemy fighters flying at more than 250 knots. Few of the fighters proved to be airworthy, and they were delivered intentionally without guns or gunsights. The Ministry of Defense of France had feared that modern types of planes would easily be captured by the German Condor Legion fighting with General Francisco Franco, and the lesser Models were a way of maintaining official "neutrality". The planes were surpassed by more modern types introduced by the end of 1936 on both sides.

The Republic circulated photos of Malraux standing next to some Potez 540 bombers suggesting that France was on their side, at a time when France and the United Kingdom had declared official neutrality. But Malraux's commitment to the Republicans was personal, like that of many other foreign volunteers, and there was never any suggestion that he was there at the behest of the French Government. Malraux himself was not a pilot, and never claimed to be one, but his leadership qualities seem to have been recognized because he was made Squadron Leader of the 'España' squadron. Acutely aware of the Republicans' inferior armaments, of which outdated aircraft were just one Example, he toured the United States to raise funds for the cause. In 1938 he published L'Espoir (Man's Hope), a novel influenced by his Spanish war experiences.

At the beginning of the Second World War, Malraux joined the French Army. He was captured in 1940 during the Battle of France but escaped and later joined the French Resistance. In 1944, he was captured by the Gestapo. He later commanded the tank unit Brigade Alsace-Lorraine in defence of Strasbourg and in the attack on Stuttgart.

During the war, he worked on his last novel, The Struggle with the Angel, the title drawn from the story of the Biblical Jacob. The manuscript was destroyed by the Gestapo after his capture in 1944. A surviving first section, titled The Walnut Trees of Altenburg, was published after the war.

Shortly after the war, General Charles de Gaulle appointed Malraux as his Minister for Information (1945–1946). Soon after, he completed his first book on art, The Psychology of Art, published in three volumes (1947–1949). The work was subsequently revised and republished in one volume as The Voices of Silence (Les Voix du Silence), the first part of which has been published separately as The Museum without Walls. Other important works on the theory of art were to follow. These included the three-volume Metamorphosis of the Gods and Precarious Man and Literature, the latter published posthumously in 1977. In 1948, Malraux married a second time, to Marie-Madeleine Lioux, a concert Pianist and the widow of his half-brother, Roland Malraux. They separated in 1966. Subsequently, Malraux lived with Louise de Vilmorin in the Vilmorin family château at Verrières-le-Buisson, Essonne, a suburb southwest of Paris. Vilmorin was best known as a Writer of delicate but mordant tales, often set in aristocratic or artistic milieu. Her most famous novel was Madame de..., published in 1951, which was adapted into the celebrated film The Earrings of Madame de… (1953), directed by Max Ophüls and starring Charles Boyer, Danielle Darrieux and Vittorio de Sica. Vilmorin's other works included Juliette, La lettre dans un taxi, Les belles amours, Saintes-Unefois, and Intimités. Her letters to Jean Cocteau were published after the death of both correspondents. After Louise's death, Malraux spent his final years with her relative, Sophie de Vilmorin.

In 1957, Malraux published the first volume of his trilogy on art entitled The Metamorphosis of the Gods. The second two volumes (not yet translated into English) were published shortly before he died in 1976. They are entitled L’Irréel and L'Intemporel and discuss artistic developments from the Renaissance to modern times. Malraux also initiated the series Arts of Mankind, an ambitious survey of world art that generated more than thirty large, illustrated volumes.

When de Gaulle returned to the French presidency in 1958, Malraux became France's first Minister of Cultural Affairs, a post he held from 1958 to 1969. On 7 February 1962, Malraux was the target of assassination attempt by the Organisation armée secrète (OAS) who set off a bomb to his apartment building that failed to kill its intended target, but did leave a four-year girl living in the adjoining apartment blinded by the shrapnel. Ironically, Malraux was a lukewarm supporter of de Gaulle's decision to grant independence to Algeria, but the OAS was not aware of this, and had decided to assassinate Malraux as a high-profile minister.

During this post-war period, Malraux published a series of semi-autobiographical works, the first entitled Antimémoires (1967). A later volume in the series, Lazarus, is a reflection on death occasioned by his experiences during a serious illness. La Tête d'obsidienne (1974) (translated as Picasso's Mask) concerns Picasso, and visual art more generally. In his last book, published posthumously in 1977, L'Homme précaire et la littérature, Malraux propounded the theory that there was a bibliothèque imaginarie where Writers created works that influenced subsequent Writers much as Painters learned their craft by studying the old masters; once they have understood the work of the old masters, Writers would sally forth with the knowledge gained to create new works that added to the growing and never-ending bibliothèque imaginarie. An elitist who appreciated what he saw as the high culture of all the nations of the world, Malraux was especially interested in art history and archaeology, and saw his duty as a Writer to share what he knew with ordinary people. An aesthete, Malraux believed that art was spiritually enriching and necessary for humanity.

Malraux was an outspoken supporter of the Bangladesh liberation movement during the 1971 Pakistani Civil War and despite his age seriously considered joining the struggle. When Indira Gandhi came to Paris in November 1971, there was extensive discussion between them about the situation in Bangladesh.

Malraux died in Créteil, near Paris, on 23 November 1976. He was buried in the Verrières-le-Buisson (Essonne) cemetery. In recognition of his contributions to French culture, his ashes were moved to the Panthéon in Paris during 1996, on the twentieth anniversary of his death.

There is now a large and steadily growing body of critical commentary on Malraux's literary œuvre, including his very extensive writings on art. Unfortunately, some of his works, including the last two volumes of The Metamorphosis of the Gods (L'Irréel and L'Intemporel) are not yet available in English translation. Malraux's works on the theory of art contain a revolutionary approach to art that challenges the Enlightenment tradition that treats art simply as a source of "aesthetic pleasure". However, as French Writer André Brincourt has commented, Malraux's books on art have been "skimmed a lot but very little read" (this is especially true in Anglophone countries) and the radical implications of his thinking are often missed. A particularly important aspect of Malraux's thinking about art is his explanation of the capacity of art to transcend time. In contrast to the traditional notion that art endures because it is timeless ("eternal"), Malraux argues that art lives on through metamorphosis – a process of resuscitation (where the work had fallen into obscurity) and transformation in meaning.