The processes involved in soil domestication have altered the soil microbial ecology. We examined the question of whether animal manure application affects the soil microbial ecology of farmlands. The effects of global animal manure application on soil microorganisms were subjected to a meta-analysis based on randomized controlled treatments. A total of 2303 studies conducted in the last 30 years were incorporated into the analysis, and an additional 45 soil samples were collected and sequenced to obtain 16S rRNA and 18S rRNA data. The results revealed that manure application increased soil microbial biomass. Manure application alone increased bacterial diversity (M-Z: 7.546 and M-I: 8.68) and inhibited and reduced fungal diversity (M-Z: -1.15 and M-I: -1.03). Inorganic fertilizer replaced cattle and swine manure and provided nutrients to soil microorganisms. The soil samples of the experimental base were analyzed, and the relative abundances of bacteria and fungi were altered compared with no manure application. Manure increased bacterial diversity and reduced fungal diversity. Mrakia frigida and Betaproteobacteriales, which inhibit other microorganisms, increased significantly in the domesticated soil. Moreover, farm sewage treatments resulted in a bottleneck in the manure recovery rate that should be the focus of future research. Our results suggest that the potential risks of restructuring the microbial ecology of cultivated land must be considered.