The fungal kingdom harbors a vast chemical repertoire that can be repurposed into pesticides, drugs, and materials. However, despite this enormous potential, fungal biosynthetic capabilities remain poorly described, largely because many genes encoding biosynthetic pathways are not expressed under artificial cultivation conditions. Here, we used post-genomic approaches to survey the biosynthetic capabilities of more than 140 plant- and insect-associated Hypocrealean fungi and mushroom-forming Basidiomycetes. We annotated thousands of biosynthetic gene clusters (BGCs), assigned putative products to more than 1,000 of them, and experimentally linked over 100 BGCs to their corresponding molecules. In parallel, we established eurotiomycete yeasts as novel heterologous hosts for fungal natural products. These hosts combine the genetic tractability of conventional yeasts with the metabolic robustness of filamentous fungi. We developed genetic engineering tools and automation protocols enabling cheap, efficient, and precise gene integration and genome editing, allowing heterologous production of several new fungal natural products. Our work highlights the vast and underexplored chemical repertoire of fungi and demonstrates the potential of black yeasts for the systematic discovery, characterization, and production of natural products. We believe this provides a strong foundation for high-throughput discovery and production of fungal natural products.