In 1929 he began studying architecture in the Department of Fine Arts at the Catholic University in Santiago. After graduating in 1931, he traveled to Europe, and in 1934 worked in Paris at Le Corbusier's atelier, where he participated in the plans for Le Corbusier's book Ville Radieuse. He then moved to Spain, where he became friends with Federico García Lorca, who gave him a letter of introduction to Salvador Dalí. When vatta returned to Paris in 1938, he consequently came into contact with the surrealist group, and began his first paintings, a series titled Morphologies psychologiques. He emigrated to the United States in 1939, sharing in the activities of refugee surrealists in New York and principally influenced by Marcel Duchamp. On a trip to Mexico, he painted a "cosmic symphony," La Terre est un Homme (1942), the starting point of his search for a new space that climaxed with Le Vertige d'Eros (1944, Museum of Modern Art, New York). Matta formed a complete mythology and cosmogony, presenting persecuted-persecutor figures in an irrational universe. From 1950 to 1955, after settling in Rome, the subjects of his paintings evolved in keeping with his social concerns and his reading. Later, after spending some time in Paris, he settled at Boissy-sans-Avoir. While remaining vehemently surrealist, Matta sought to express his political engagement, protesting against "blinders, glorified habits, killers of freedom." He painted large pamphlet-paintings—such as La Banale de Venise (1956), ridiculing the Venice Biennial in a grotesque style; or Cina Cita (1963), deriding Italian cinema circles—and created triptychs and polyptychs on progressive themes. Evoking the saga of mankind in L'Espace de l'espèce (1959-67), he denounced the Vietnam war and napalm bombings in Sur l'État de l'Union (1964-5, Galerie lolas, Paris) and Burn Baby Burn (1965-6). An enthusiastic trip to Cuba inspired the series Cuba Frutto bomba, which he presented in Rome and Paris. He advanced a "hyper-technique" that allowed him to execute huge revolutionary compositions in just a few hours, exhibiting a few examples in his show Être avec, in 1967, at the Musée de Saint-Denis.
Matta's boundless ambition led him to compose colossal frescoes, including six 65-foot-long works on the theme of the Great Abolitionist, which he showed in 1975 at the Museum of Modern Art in Mexico City. He repeated the feat at the Palazzo del Popolo at Todi, in 1984, with 30-foot-long paintings, such as Coïgitum. This taste for the colossal resulted in some of his least interesting work, but is easily explained by his determination to create a cosmic art. For his retrospective at the Centre Georges-Pompidou (October 3-December 16, 1985), Matta made this recommendation: "The paintings should be presented like cartographies of human nature and its energies." The last exhibition of his work held in his lifetime, in April 2000 at the Galerie Claude Bernard, titled L'Année des trois 000, attested to the permanence of his obsessions in his small paintings, done at the age of eighty-nine. "I am not someone who paints, I am someone who shows," claimed Matta, who had succeeded in showing aspects of the microcosm as well as the macrocosm.