Even though Altolaguirre lost his brother Luis and his half- brother Federico - both shot by the Republicans in the first months of the war -he always remained faithful to the cause of the Republic.
He collaborated with El Mono Azul, the newsletter of the Alliance of Anti-Fascist Writers, who also appointed him director of the Teatro Español. He had already written three unpublished plays Amor de dos vidas (1932), Entre dos públicos (1933-1934), and Castigadme si queréis (1933-1934), and now, supported by several of the actors of La Barraca, he started working as stage director, performing several plays by Cervantes in the war fronts near the Spanish capital.

In the winter of 1936, he moved to Valencia, where he joined the group of poets and artists that had been publishing Hora de España since January 1937: Juan Gil-Albert, Arturo Sánchez Barbudo, Ramón Gaya, Luis Cernuda, Emilio Prados and Arturo Serrano Plaja, among others. Altolaguirre also printed several volumes coinciding with the International Congress of Anti-Fascist Writers (Valencia, 1937): the anthology Poetas en la España leal, and the books Bajo tu clara sombra y otros poemas, by Octavio Paz, Momento español, by Juan Marinello, and España: poema en cuatro angustias y una esperanza,by Nicolás Guillén.

In Valencia, Altolaguirre continued his career in the theater. His play, El triunfo de las Germanías, written in collaboration with Bergamín, had its premiere in January of 1937. Later, during the Congress, he was stage director of García Lorca’s Mariana Pineda. In July of 1938, he joined the ranks in the Aragon front, where he printed the newspaper of XI Corps of the Army of the East. In August, he and Juan Gil-Albert printed the literary pamphlet Granada de las letras y de las armas in a printing shop installed at the Monastery of Gualter. In November, he began working in the old printing shop at the Monastery of Montserrat, where he edited the magazine Los Lunes de El Combatiente (1938-1939, and the books Cancionero menor para los combatientes (1936-1938), by Emilio Prados, España en el corazón (1938), by Pablo Neruda, and España, aparta de mí este cáliz (1939), by César Vallejo.

In the first days of February 1939, physically and morally devastated from war, Altolaguirre abandoned Spain. After crossing the border he arrived a t a concentration camp in Perpignan, where he suffered a nervous breakdown. Thanks to the intervention of the French Antifascists Writer Association, he soon managed to join his wife and sister in Paris. In march, with the help of Paul Éluard, Pablo Picasso and other friends living in the French capital, the Altolaguirre couple escaped from Europe and fleet into an exile that would first take them to Cuba and then to Mexico.