East Siberia’s permafrost contains about 500 GtC of frozen highly labile carbon deposits, a so-called Yedoma. Using a permafrost carbon cycle model we analyzed mobilization of this huge carbon stock in a future warming. Conditions necessary to trigger the irreversible Yedoma thawing maintained by deep respiration and methanogenesis are studied. Once started, this process could release 2.0–2.8 GtC yr−1 during years 2300–2400 transforming 75% of initial carbon stock into CO2 and methane. The time when the fast deep-soil decomposition starts is inversely proportional to the warming rate, while the corresponding (critical) temperature anomaly slightly increases at larger warming rates. This second-order effect is due to the deep-soil heat storage caused by external warming, which leads to more homogeneous soil heating when the warming is slower, and so a smaller external warming is needed to thaw the permafrost. The effect of specific microbial heat that accompanies oxic decomposition is of comparable importance to that of the warming rate on the critical temperature anomaly, while it is of minor importance on the time when deep decomposition starts.