Soil organic carbon (SOC) decomposition underpins soil-atmosphere carbon exchange and is regulated by climate change-mediated variations in soil redox conditions. Periodic anoxia, commonly occurring following precipitation, soil flooding, and erosion events, is assumed to preserve SOC. Yet, water saturation may also increase SOC decomposition relative to unsaturated conditions, and contradictory findings among previous studies remain unexplained. Here, using incubation experiments on 20 soils collected across a 24° latitude gradient in China, we show that 70% of the soils showed a higher or similar anoxic decomposition rate of SOC compared to the oxic treatment, indicating fast SOC loss under relatively short anoxia. Methane production was far lower than CO2 due to the presence of alternative terminal electron acceptors (TEAs). Variation in alternative TEAs and microbial community shows that fast anoxic decomposition was primarily driven by iron (Fe) reduction, which accounted for up to 90% of anoxic CO2 production. Meanwhile, positive relationships among water-extractable organic carbon (OC), hydrochloric acid-extractable ferrous Fe, relative abundance of Fe-reducing prokaryotes, and the SOC decomposition rate suggest the release of readily metabolized substrates following Fe reduction. This release provided substrates for anoxic metabolism and potentially led to the loss of OC protected by Fe (Fe-bound OC; a slow-cycling OC pool under oxic conditions). Mass balance calculation confirms that Fe-bound OC loss was mostly similar to elevated anoxic SOC decomposition in magnitude, and random forest modeling indicates that soils rich in reducible Fe, SOC, and Fe-reducing prokaryotes most likely experience elevated SOC decomposition under periodic anoxia. Overall, our findings demonstrate that fast anoxic decomposition of SOC is a potentially important pathway that may stimulate SOC loss under climate change-mediated intense hydrologic regimes, particularly for soils rich in reducible Fe and SOC.