Aspergillus, one of the most product-rich and genetically robust genera, contains a diverse range of species with potential economic and ecological implications. Chemically, Aspergillus is one of the essential sources of polyketides, alkaloids, diphenyl ethers, diketopiperazines, and other miscellaneous compounds, displaying a variety of pharmacological activities. The α-pyrones are unsaturated six-membered lactones. Although α-pyrone has a small structure, it is responsible for the structural diversity of several natural and synthetic compounds and multiple biological activities. In this review, we have summarized approximately 178 α-pyrone containing metabolites derivatives identified/reported from terrestrial, marine, endophytic, and filamentous Aspergillus species, including their sources, biological properties, and biosynthetic pathways until mid-2023, for the first time. This review is the first to compile and analyze the available data on α-pyrone metabolites from Aspergillus, which could facilitate further research and innovation in this field. Additionally, it offers a valuable source of scaffolds for future bioactive drug development, as some of these metabolites have shown potent antimicrobial, anti-inflammatory, and anticancer effects. Therefore, this review has significant implications for the advancement of natural product chemistry, pharmacology, biotechnology, and medicine.