Soil microbes play an integral role in agricultural production, and there is limited understating of the complex responses of microbial diversity to organic and conventional farming. Here we report the response of soil microbiome, of a paddy field, to ten years application of inorganic fertilizer (CF) and organic fertilizer (OF), also including a no fertilizer control (CK). The bacterial and fungal communities were examined using high-throughput sequencing. Our results revealed that compared with CK and OF, the CF treatment had lower richness of bacteria, but higher richness of fungi. To utilize the fertilizers efficiently and adaptions to soil conditions, bacterial and fungal compositions changed under different fertilizations. The application of CF increased the abundance of some oligotrophic bacteria such as Bacteroidetes and Acidobacteria, and increased the relative abundance of Zygomycota phylum of fungi. The application of OF increased the abundance of the copiotrophic bacteria such as Proteobacteria phylum, and the relative abundance of Agaricomycetes and Orbiliomycetes classes of fungi. The OF also had the sparsest and most discrete network indicated that soil microbes tended to be less interacted with each other after organic fertilizers inputs. This study suggested that the soil microorganisms respond differently to the inputs of inorganic and organic fertilizers in paddy soil, which offers novel insights into the potential of managing soil microbiomes for sustainable agricultural productivity.