The mushroom cultivation industry is increasingly integrating agricultural and agro-industrial by-products as sustainable alternative substrates to mitigate reliance on traditional raw materials (e.g., hardwood sawdust and wheat straw) and address environmental concerns associated with agricultural waste management. Edible and medicinal mushrooms, through their specialized lignocellulolytic enzyme systems (including laccases, manganese peroxidases, and cellulases), possess the unique capability to bioconvert complex lignocellulosic biomass into nutrient-rich protein food sources. This review comprehensively examines the major categories of agricultural by-products—ranging from crop residues (cereal straws, corn cobs, sugarcane bagasse) and processing by-products (cottonseed hulls, beet pulp, soybean meal) to forestry residues—utilizable for commercial mushroom production. We analyze the critical physicochemical factors influencing bioconversion efficiency, including the Carbon-to-Nitrogen (C/N) ratio, substrate moisture, pH, porosity, and lignin-to-cellulose ratios. Strategies for optimizing biological efficiency (BE) and yield are systematically discussed, focusing on physical/chemical pre-treatments, optimal biological supplementation, and substrate formulation blending. Furthermore, recent research trends in Korea such as bottle culture substrate formulation for Pleurotus eryngii and Flammulina velutipes, energy-saving pasteurization techniques, and spent mushroom substrate (SMS) upcycling—are integrated alongside future perspectives on circular bioeconomy.