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Knowledge of microbial mechanisms is critical to understand Earth's biogeochemical cycle under climate and environmental changes. However, large uncertainties remain in model simulations and predictions due to the lack of explicit parameterization of microbial data and few applications beyond the laboratory. In addition, most experimental and modeling studies of warming-induced changes in soil carbon (C) focus on temperature sensitivity, neglecting concomitant effects of changes in soil moisture. Soil microbes are sensitive to moisture, and their responses can dramatically impact soil biogeochemical cycles. Here we represent microbial and enzymatic functions in response to changes in moisture in the Microbial-ENzyme Decomposition (MEND) model. Through modeling with long-term field observations from subtropical forests, we demonstrate that parameterization with microbial data in addition to respiration fluxes greatly increases confidence in model simulations. We further employ the calibrated model to simulate the responses of soil organic C (SOC) under multiple environmental change scenarios. The model shows significant increases in SOC in response to decreasing soil moisture and only minor changes in SOC in response to increasing soil temperature. Increasing litter inputs also cause a significant increase in SOC in the pine forest, whereas an insignificant negative effect is simulated in the broadleaf forest. We also demonstrate the co-metabolism mechanism for the priming effects, i.e., more labile inputs to soil could stimulate microbial and enzymatic growth and activity. Our study provides strong evidence of microbial control over soil C decomposition and suggests the future trajectory of soil C may be more responsive to changes in soil moisture than temperature, particularly in tropical and subtropical environments.