Soil organic carbon (SOC) is the largest terrestrial carbon pool, but it is still uncertain how it will respond to climate change. Specifically, the fate of SOC due to concurrent changes in soil temperature and moisture is uncertain. It is generally accepted that microbially driven SOC decomposition will increase with warming, provided that sufficient soil moisture (and hence sufficient C substrate) is available for microbial decomposition. We use a mechanistic, microbially explicit SOC decomposition model, the Jena Soil Model (JSM), and focus on the depolymerisation of litter and microbial residues by microbes at different soil depths as well as the sensitivities of the depolymerisation of litter and microbial residues to soil warming and different drought intensities. In a series of model experiments, we test the effects of soil warming and droughts on SOC stocks, in combination with different temperature sensitivities (Q10 values) for the half-saturation constant Km (Q10,Km) associated with the breakdown of litter or microbial residues. We find that soil warming can lead to SOC losses at a timescale of a century and that these losses are highest in the topsoil (compared with the subsoil). Droughts can alleviate the effects of soil warming and reduce SOC losses, by posing strong microbial limitation on the depolymerisation rates, and even lead to SOC accumulation, provided that litter inputs remain unchanged. While absolute SOC losses were highest in the topsoil, we found that the temperature and moisture sensitivities of Km were important drivers of SOC losses in the subsoil - where microbial biomass is low and mineral-associated OC is high. Furthermore, a combination of drought and different Q10,Km values associated with different enzymes for the breakdown of litter or microbial residues had counteracting effects on the overall SOC balance. In this study, we show that, while absolute SOC changes driven by soil warming and drought are highest in the topsoil, SOC in the subsoil is more sensitive to warming and drought due to the intricate interplay between Km, temperature, soil moisture, and mineral-associated SOC.