The dominant fusarium species and populations causing Fusarium head blight have been shifting on a global scale, a phenomenon that has increasingly been attributed to climate change. In other systems, similar changes have led to the emergence of new diseases and previously unknown secondary metabolites (SMs) that act as toxins and virulence factors. While recent work has shown that Fusarium populations on a global scale show patterns of long-distance dispersal and recent shifts, the secondary metabolites associated with these dynamics have remained unclear. We have mapped a new class of SM, isocyanides, across the fungal kingdom. Isocyanides have previously been associated with grass pathogens and ill-thrift disease in animals that consume them. We have demonstrated that these clusters are significantly enriched in Fusarium species, raising questions about their role in fungal pathogenesis. We use a dataset of ~450 genomes to explore population-specific variants of canonical SMs and of Isocyanides. We identify population-specific variants of many SMs, raising concerns about the coupling of emerging populations with emerging mycotoxins. To better understand the threat posed by understudied toxins, we perform molecular manipulation of a highly conserved isocyanide gene cluster and demonstrate that this cluster may be linked to disease progression in wheat heads. Overall, our results identify a significant reservoir of chemical diversity within and between F. graminearum populations that contributes to FHB progression and emphasizes a need to define emerging mycotoxins.