In 1937—one year after the Fascist “conquest” of Ethiopia—the Italian East African Empire was on the brink of an economic and food crisis. In order to feed the newborn empire's growing Italian population, Mussolini's regime launched a call for agricultural mobilization meant to rapidly make the empire self-sufficient in wheat, the main staple of the Italian population. This article analyzes the scientific foundations of the program of imperial “wheat autarky” and its materialization during the “wheat campaigns” between 1938 and 1941, particularly focusing on the introduction of and experimentation with hybrid wheat seeds in the Ethiopian highlands. The article shows the key role played by Italian agronomists and plant breeders in the framing and implementation of wheat autarky in the Fascist empire. Contrary to the historical emphasis of Fascist propaganda on the technological and human colonization of Ethiopia by Italian agriculture, the article also argues for the crucial position of indigenous farming within the colonial project of wheat development. Finally, Ethiopia's environments and its nonhuman actors became essential protagonists in the unfolding of these agricultural plans. The article makes the case for viewing wheat rust—a fungal plant disease—as a key component of the evolution and demise of the Italian occupation of Ethiopia.