Soil moisture and temperature are known to be the two environmental constraints regulating mineralization of soil organic carbon (SOC). However, it remains unclear to what extent the moisture, temperature, and other abiotic and biotic factors affect the mineralization of SOC across broad geographic regions. Here, we examined the effects of multiple abiotic and biotic factors on SOC mineralization across 12 widespread arid and semiarid ecosystems on the Mongolia plateau, by using an integrative approach combining short-term laboratory incubations (28-day), field survey, and structure equation modeling (SEM). Our results showed that soil moisture had a predominant control on SOC mineralization across all sites. The average CO₂ emissions over all sites increased by 23 % from 30 to 60 % water filled pore space (WFPS) and by 176 % from 60 to 90 % WFPS. Under conditions of 25 °C and 60 % WFPS, the cumulative CO₂–C emissions in the topsoil (0–20 cm) diminished in the following order: meadow steppe (227 mg kg⁻¹) > typical steppe (216 mg kg⁻¹) > desert (99 mg kg⁻¹) > desert steppe (72 mg kg⁻¹). The temperature sensitivity of SOC mineralization (Q₁₀), the proportional change in carbon mineralization rate given a 10 °C temperature gradient, was highest under conditions of low temperature and high moisture, but it was lowest under high temperature and low moisture. The SEM analyses demonstrate that the mineralization potential of SOC seems to be directly regulated by microbe activity and substrate availability. Climatic factors (e.g. mean annual precipitation, mean annual temperature), above- and belowground biomass, and soil pH, which regulate SOC and microbial biomass carbon content, also indirectly influence the SOC mineralization. Our results indicate that global climate change, particularly the increase in the frequency of extreme storms and droughts, will substantially affect SOC mineralization and ecosystem carbon cycle in arid and semiarid regions.