Regarding the composting of rural waste, numerous studies either addressed the composting of a single waste component or were conducted at a laboratory/pilot scale. However, far less is known about the mixed composting effect of multi-component rural waste on a large scale. Here, we examined nutrient transformation, maturity degree of decomposition, and succession of microbial communities in large-scale (1,000 kg mixed waste) compost of multi-component wastes previously optimized by response models. The results showed that multi-component compost can achieve the requirement of maturity and exhibit a higher nutritional value in actual compost. It is worth noting that the mixed compost effectively removed pathogenic fungi, in which almost no pathogenic fungi were detected, and only two pathogenic bacteria regrown in the cooling and maturation stages. Structural equation models revealed that the maturity (germination index and the ratio of ammonium to nitrate) of the product was directly influenced by compost properties (electrical conductivity, pH, total organic carbon, moisture, temperature, and total nitrogen) compared with enzymes (cellulase, urease, and polyphenol oxidase) and microbial communities. Moreover, higher contents of total phosphorus, nitrate-nitrogen, and total potassium were conducive to improving compost maturity, whereas relatively lower values of moisture and pH were more advantageous. In addition, compost properties manifested a remarkable indirect effect on maturity by affecting the fungal community (Penicillium and Mycothermus). Collectively, this evidence implies that mixed compost of multi-component rural waste is feasible, and its efficacy can be applied in practical applications. This study provides a solution for the comprehensive treatment and utilization of rural waste.