Pleistocene Yedoma permafrost contains nearly a third of all organic matter (OM) stored in circum-arctic permafrost and is characterized by the presence of massive ice wedges. Due to its rapid formation by sediment accumulation and subsequent frozen storage, Yedoma OM is relatively well preserved and highly biologically available (biolabile) upon thaw. A better understanding of the processes regulating Yedoma degradation is important to improve estimates of the response and magnitude of permafrost carbon feedbacks to climate warming. In this study, we examine the composition of ice wedges and the influence of ice wedge thaw on the biolability of Yedoma OM. Incubation assays were used to assess OM biolability, fluorescence spectroscopy to characterize the OM composition, and potential enzyme activity rates to examine the controls and regulation of OM degradation. We show that increasing amounts of ice wedge melt water in Yedoma-leached incubations enhanced the loss of dissolved OM over time. This may be attributed to the presence of low-molecular weight compounds and low initial phenolic content in the OM of ice wedges, providing a readily available substrate that promotes the degradation of Yedoma OC. The physical vulnerability of ice wedges upon thaw (causing irreversible collapse), combined with the composition of ice wedge-engrained OM (co-metabolizing old OM), underlines the particularly strong potential of Yedoma to generate a positive feedback to climate warming relative to other forms of non-ice wedge permafrost.