In the boreal region, soil organic carbon (OC) dynamics are strongly governed by the interaction between wildfire and permafrost. Using a combination of field measurements, numerical modeling of soil thermal dynamics, and mass-balance modeling of OC dynamics, we tested the sensitivity of soil OC storage to a suite of individual climate factors (air temperature, soil moisture, and snow depth) and fire severity. We also conducted sensitivity analyses to explore the combined effects of fire-soil moisture interactions and snow seasonality on OC storage. OC losses were calculated as the difference in OC stocks after three fire cycles (~500 yr) following a prescribed step-change in climate and/or fire. Across single-factor scenarios, our findings indicate that warmer air temperatures resulted in the largest relative soil OC losses (~5.3 kg C m⁻²), whereas dry soil conditions alone (in the absence of wildfire) resulted in the smallest carbon losses (~0.1 kg C m⁻²). Increased fire severity resulted in carbon loss of ~3.3 kg C m⁻², whereas changes in snow depth resulted in smaller OC losses (2.1–2.2 kg C m⁻²). Across multiple climate factors, we observed larger OC losses than for single-factor scenarios. For instance, high fire severity regime associated with warmer and drier conditions resulted in OC losses of ~6.1 kg C m⁻², whereas a low fire severity regime associated with warmer and wetter conditions resulted in OC losses of ~5.6 kg C m⁻². A longer snow-free season associated with future warming resulted in OC losses of ~5.4 kg C m⁻². Soil climate was the dominant control on soil OC loss, governing the sensitivity of microbial decomposers to fluctuations in temperature and soil moisture; this control, in turn, is governed by interannual changes in active layer depth. Transitional responses of the active layer depth to fire regimes also contributed to OC losses, primarily by determining the proportion of OC into frozen and unfrozen soil layers.