Masson was born in Balagny-sur-Thérain, Oise, but was brought up in Belgium. He began his study of art at the age of eleven in Brussels, at the Académie Royale des Beaux-Arts under the guidance of Constant Montald, and later he studied in Paris. He fought for France during World War I and was seriously injured.
His early works display an interest in cubism. He later became associated with surrealism, and he was one of the most enthusiastic employers of automatic drawing, making a number of automatic works in pen and ink. Masson would often force himself to work under strict conditions, for example, after long periods of time without food or sleep, or under the influence of drugs. He believed forcing himself into a reduced state of consciousness would help his art be free from rational control, and hence get closer to the workings of his subconscious mind. Masson experimented with altered states of consciousness with artists such as Antonin Artaud, Michel Leiris, Joan Miró, Georges Bataille, Jean Dubuffet, and Georges Malkine, who were neighbors of his studio in Paris.
From around 1926 he experimented by throwing sand and glue onto canvas and making oil paintings based around the shapes that formed. By the end of the 1920s, however, he was finding automatic drawing rather restricting, and he left the surrealist movement and turned instead to a more structured style, often producing works with a violent or erotic theme, and making a number of paintings in reaction to the Spanish Civil War (he associated once more with the surrealists at the end of the 1930s).