Senger rose through the ranks, serving at the cavalry school in Hanover (1919–1921) and then as chief of staff of the Cavalry Inspectorate. An opponent of the "all-tank" theorists, Senger supported development of mechanized infantry (panzergrenadiers). In March 1939, he was promoted to colonel and given command of a regiment, which he later led in the invasion of Poland. He commanded a mechanized brigade in the invasion of France in 1940. Senger's cosmopolitan background led to his appointment as chief of the German delegation to the Franco-Italian armistice commission following the surrender of France.
In September 1941, Senger was promoted to Generalmajor (U.S. equiv. brigadier general), and he commanded the 17th Panzer Division. He led the division in Operation barbarossa and Field Marshal Erich von Manstein's subsequent offensive in the Ukraine. In 1943, doubts about the capability of Italian troops led to Senger's promotion to Generalleutnant (U.S. equiv. major general) and reassignment to coordinate Axis strategy in Sicily. He remained in Italy for the remainder of the war and led German troops in several significant battles, including the withdrawal from Sardinia and Corsica and the Battle of Monte Casino.
Promoted to General der Panzertruppen (U.S. equiv. lieutenant general) in January 1944, Senger oversaw the negotiations that led to the surrender of German forces in Italy in May 1945. Held as a prisoner of war from 1946 to 1948, on his release Senger became the headmaster of Salem, a public school near Lake Constance. During the 1950s, he advised Federal Republic of Germany President Konrad Adenauer on rearmament and the formation of the new German army, the Bundeswehr. Senger died in Freiburg on 4 January 1963.
Senger und Etterlin, Ferdinand von, and Stefan Senger und Etterlin. "General Frido von Senger und Etterlin." In Correlli Barnett, ed., Hitler's Generals, 375–392. New York: Grove Weidenfeld, 1989.; Senger und Etterlin, Frido von. Krieg in Europa. Cologne: Kiepenheuer and Witsch, 1960.