[Objectives] The objective of this study was to investigate the effects of different organic fertilizers partial substitution for chemical fertilizer on crop yield and its components, and soil microbiome in a rice-wheat cropping system, and find out the suitable fertilizer regime to increase crop yield and provide the theoretical basis for establishing high-productivity associated soil microbiome. [Methods] With the long-term fertilizer experimental site located in Jintan, Jiangsu as the research site, six fertilizer regimes were included in this study:no fertilizer(CK), conventional dosage of chemical fertilizer (NPK),3 000 kg·hm-2 pig manure organic fertilizer substituted 30% of chemical fertilizer (NPKM1), 6 000 kg·hm-2 pig manure organic fertilizer substituted 50% of chemical fertilizer (NPKM2), 1 800 kg·hm-2 pig manure organic-inorganic compound fertilizer substituted 50% of chemical fertilizer(NPKMOI1), and 3 600 kg·hm-2 pig manure organic-inorganic compound fertilizer substituted 70% of chemical fertilizer (NPKMOI2). The number of productive spikes, number of grains per spike,thousand grains weight, theoretical yield,and actual yield of rice and wheat were measured, respectively. Soil microbial biomass and soil microbiome were determined by chloroform fumigation-K2SO4 extraction method and high-throughput sequencing. [Results] Compared to the NPK treatment, pig manure organic fertilizer (NPKM1, NPKM2) and pig manure organic-inorganic compound fertilizer(NPKMOI1, NPKMOI2)substituted partial chemical fertilizer had no significant decline in rice and wheat yield and their components, and enhanced soil microbial biomass carbon and nitrogen. NPKMOI1 and NPKMOI2 treatments increased soil bacterial richness, diversity and evenness,and markedly shaped the soil bacterial community,and such shifts were increased with the increase of substitution amount of chemical fertilizer.[Conclusions] The treatment that 3 600 kg·hm-2 pig manure organic-inorganic compound fertilizer substituted 70% of chemical fertilizer was a potential fertilization regime to enhance crop yield and establish high-productivity associated soil microbial community. [ABSTRACT FROM AUTHOR]