A political activist since his youth, Siqueiros studied at the San Carlos Academy of Fine Arts, Mexico City, before leaving in 1913 to fight in the army of Venustiano Carranza during the Mexican Revolution. Later he continued his art studies in Europe.

In 1922, after returning to Mexico, Siqueiros helped paint the frescoes on the walls of the National Preparatory School and also began organizing and leading unions of artists and workingmen. During the Spanish Civil War (1936–39), he commanded several brigades for the Republicans. Over four decades, his labour-union work and his communist political activities led to numerous jailings and periods of exile. He visited the United States, the Soviet Union, and many Latin American countries as a lecturer and guest artist.

Most of Siqueiros's large murals are in government buildings in Mexico. His murals are distinguished by great dynamism and compositional movement, monumental size and vigour, sculptural treatment of forms, and a limited colour range that is subordinated to dramatic effects of light and shadow. Siqueiros and his followers produced thousands of square metres of vivid wall paintings in which numerous social, political, and industrial changes were portrayed from a left-wing perspective. He commonly used synthetic lacquer colours sprayed from paint guns in order to speed up the process of decorating large public buildings. He also did many easel paintings, the best-known of which is perhaps Echo of a Cry (1937).