A 7-year multisite field experiment was performed to assess the relative importance of climate, soil, and microbial properties of crop production in a wheat cropping system under contrasting fertilization management (i.e., continuous organic vs. chemical fertilization). The results showed that continuous organic application increased the annual grain yield and soil organic carbon by an average of 13.2% and 38.0%, respectively, compared to chemical fertilization. Continuous organic application increased the soil pH, which led to a significant increase in bacterial richness (i.e., Chao1) and diversity (i.e., Shannon index). Notably, organic application favored the growth of Proteobacteria and Actinobacteria but reduced the abundances of Bacteroides, Verrucomicrobia, and Acidobacteria, which ultimately led to a more complicated bacterial co-occurrence network. Importantly, organic application increased the abundances of functional genes involved in C fixation (e.g., sdhD, ACO, and acsB), C degradation (e.g., pulA, celC, and CBH2), N fixation (e.g., anfG and amoC) and nitrification (e.g., nifK), as well as P transporters (e.g., ugpQ and phnC). The structural equation modeling (SEM) results indicated that the annual air temperature and soil pH under chemical fertilizer treatment and the bacterial community structure and functional gene abundance under treatment with organic application were the primary drivers of the yield performance. Variance partitioning analysis further revealed that under chemical fertilization, climate, soil, the bacterial community, and potential function explained 32.0%, 26.7%, 19.9% and 21.4%, respectively, of the overall variance in crop productivity; however, these values shifted to 16.6%, 8.3%, 34.5% and 40.6%, respectively, when organic fertilizer was applied. These findings suggest that continuous organic application reduces the contribution of climate and edaphic conditions to crop yield compared to chemical fertilization but strengthens the associations between soil microbial function and crop production. Overall, this work provides new insights into the complexity of fertilization-induced climate-plant-microbial interactions and highlights the importance of intensified biological interactions for the sustainability of cropping ecosystems.