Nigeria generates enormous volumes of agricultural waste annually, including cassava peels, rice husk, sugarcane bagasse, corn cobs, palm empty fruit bunches, and sorghum stalks. Inefficient disposal of these residues contributes to greenhouse gas emissions, soil degradation, and public health burdens. Enzymatic biodegradation offers a sustainable and cost-effective strategy for the valorisation of these lignocellulosic materials into fermentable sugars, biofuels, pharmaceutical precursors, and other high-value products. This review critically examines the advances in the enzymatic biodegradation of agricultural waste in Nigeria, with emphasis on key enzyme systems, cellulases, hemicellulases, laccases, lignin peroxidases, and manganese peroxidases, and the microorganisms responsible for their production. The role of solid-state fermentation (SSF) and submerged fermentation (SmF) as platforms for enzyme production is discussed, along with physicochemical parameters influencing enzyme activity and yield. The biotechnological applications of these enzymatic processes, particularly bioethanol production, bioremediation, and the synthesis of pharmaceutical-grade compounds, are highlighted. Current challenges, including high enzyme production costs, substrate recalcitrance, and limited scale-up infrastructure in Nigeria, are identified, alongside emerging strategies such as enzyme engineering, consolidated bioprocessing (CBP), and the circular bioeconomy model. This review identifies critical gaps in Nigerian-specific enzyme biotechnology research and recommends targeted policy, investment, and translational pathways to unlock the full potential of the country’s agricultural waste biomass.