New biotic stresses have emerged around the globe over the last decades threatening food safety and security. In 2016, scientists confirmed the presence of the devastating wheat-blast disease in Bangladesh, South Asia–its first occurrence outside South America. Severely blast-affected wheat fields had their grain yield wiped out. This poses a severe threat to food security in a densely-populated region with millions of poor inhabitants where wheat is a major staple crop and per capita wheat consumption has been increasing. As an ex ante impact assessment, this study examined potential wheat-blast scenarios in Bangladesh, India, and Pakistan. Based on the agro-climatic conditions in the epicenter, where the disease was first identified in Bangladesh in 2016, this study identified the correspondingly vulnerable areas in India, Pakistan and Bangladesh amounting to 7 million ha. Assuming a conservative scenario of 5–10% for blast-induced wheat production loss, this study estimated the annual potential wheat loss across the sampled countries to be 0.89–1.77 million tons, equivalent to USD 132–264 million. Such losses further threaten an already-precarious national food security, putting pressure on wheat imports and wheat prices. The study is a call for action to tackle the real wheat-blast threat in South Asia.