This chapter provides a comprehensive exploration of the diversity, systematics, and chemical insights of seven key genera of macrofungi; Antrodia, Auricularia, Hericium, Lentinus, Morchella, Pleurotus, and Schizophyllum from Ascomycota and Basidiomycota. These fungi play vital roles in ecosystem processes, such as nutrient cycling, and symbiotic interactions with plants. The chapter reviews their distribution, classification, morphological characteristics, and ecological significance, emphasizing the taxonomic challenges and ongoing discoveries in fungal diversity. Additionally, the bioactive compounds found in these fungi, including terpenoids, polyphenols, and polysaccharides, are documented for their therapeutic properties, demonstrating their importance in pharmaceuticals, nutraceuticals, and functional foods. The study highlights the vast diversity and importance of macrofungi with respect to their applications in sustainable agriculture.