A new and severe disease of maize caused by a previously unknown fungal pathogen, Cochliobolus carbonum race 1, was first described in 1938. The molecular events that led to the sudden appearance of this disease are described in this paper. Resistance to C. carbonum race 1 was found to be widespread in maize and is conferred by a pair of unlinked duplicate genes, Hm1 and Hm2. Here, we demonstrate that resistance is the wild-type condition in maize. Two events, a transposon insertion in Hm1 and a deletion in Hm2, led to the loss of resistance, resulting in the origin of a new disease. None of the other plant species tested is susceptible to C. carbonum race 1, and they all possess candidate genes with high homology to Hm1 and Hm2. In sorghum and rice, these homologs map to two chromosomal regions that are syntenic with the maize Hm1 and Hm2 loci, indicating that they are related to the maize genes by vertical descent. These results suggest that the Hm-encoded resistance is of ancient origin and probably is conserved in all grasses.