The extensive accumulation of spent mushroom substrate (SMS) owing to the large-scale production of edible fungi is causing environmental problems that cannot be ignored. Co-composting is a promising method for agricultural and animal husbandry waste disposal. In this study, the composition and function of microbial communities in the process of cattle manure–maize straw composting with SMS addition were compared through an integrated meta-omics approach. The results showed that irrespective of SMS addition, the predominant fungi were Ascomycota, while the dominant bacteria were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. High temperature promoted the evolution from Gram-negative bacteria (Bacteroides, Proteobacteria) to Gram-positive bacteria (Firmicutes, Actinomycetes). The composting process was accelerated by SMS addition, and the substrate was effectively degraded in 14 days. Metaproteomics results showed that the dominant microorganism, Planifilum fulgidum, secreted large amounts of S8, M17, and M32 proteases that could degrade macromolecular protein substrates in the presence of SMS. Planifilum fulgidum, along with Thermobifida fusca and Melanocarpus albomyces, synergistically degraded hemicellulose, cellulose, and protein. In addition, the dominant microorganisms related to the initial raw materials such as Pichia, Lactobacillus in the microbial agent and Hypsizygus in SMS could not adapt to the high-temperature environment (>60 °C) and were replaced by thermophilic bacteria after 5 days of composting.