Lewis was born on a yacht off the Canadian island of Nova Scotia. His mother was British, his father American. He went to school in England, first at Rugby school, then at the Slade School of art in London, before spending most of the 1900s travelling around Europe and studying art in Paris.
It was in the 1910s that he found the painting style for which he is best known today, a style which his friend Ezra Pound dubbed vorticism. Lewis found the strong structure of cubism painting appealing, but said it did not seem "alive" compared to futurist art, which, conversely, lacked structure. Vorticism is often seen as a combination of these two movements.
After the vorticists only exhibition in 1915, the movement broke up, largely as a result of World War I. Lewis was posted to the western front, and served as Official War Artist, painting one of his best known paintings, A Battery Shelled, while there.
By the late 1920s, Lewis was not painting so much, instead concentrating on writing. He wrote biting satirical attacks on the Bloomsbury group, which did not help him to be accepted into the literary world, and his book Hitler (1931), which was distinctly in favour of its subject, caused him to be shunned by many. His associating with the British Fascist Party did not help. He later wrote The Hitler Cult (1939), a book which largely went back on his earlier pro-Hitler pronouncements, but the damage was done, and Lewis was to remain an isolated figure.
Despite being better known for his writing than his painting in his later years, paintings from the 1930s and 1940s constitute some of his best known work. They are mainly portraits, and include pictures of Edith Sitwell (1935), T. S. Eliot (1938 and again in 1949) and Ezra Pound (1938).
Lewis spent World War II in the United States and Canada. He returned to England following the war. By 1951, he was completely blind, and in 1954 he wrote the autobiographical Rude Assignment. He died in 1957.