He was in Madrid on 17 July 1936 when the military insurrection against the Republican government began and had to quickly escape to Burgos, where he joined the Nationalist forces under Franco.

During the war, he held various major military appointments including chief of general staff of the Castillian Army Corps during the Brunete offensive in July 1937 and the subsequent Battle of Teruel between December 1937 and February 1938.

In May 1940, a year after the civil war had ended, he was promoted to brigadier-general in command of the Army General Staff of Morocco and Military Region IV.

After Hitler launched Operation Barbarossa against the Soviet Union in June 1941, Franco's government authorized the dispatch of a volunteer Spanish division under the overall command of the German Wehrmacht.

However, despite being popular with his soldiers, Muñoz Grandes behavior began to show too much of a "pro-German slant" for Franco who, even in mid-1942, was preoccupied with the general direction and possible outcome of the war.

Esteban Infantes was close friend of the Minister of War, General José Enrique Varela, and for several months he had been pressing for a transfer to a combat role with the Blue Division.

Consequently, Esteban Infantes was dispatched to Germany where he was inducted into the Wehrmacht with the rank of Generalmajor and with the military oath being administered directly to Hitler at the Berghof.

The German generals also initially considered him to be too anglophile in his outlook but Esteban Infantes soon won their respect as he began to demonstrate his considerable skill as a great military planner especially in more counter-offensive situations that developed on the Eastern Front during 1943.