Interactions between minerals and organic carbon (OC) in soils are key to stabilize OC and mitigate greenhouse gas emissions upon permafrost thaw. However, changes in soil water pathways upon permafrost thaw are likely to affect the stability of mineral OC interactions by inducing their dissolution and precipitation. This study aims to assess and quantify how mineral OC interactions are affected by dissolution and precipitation in thawed relative to unthawed layers. We hypothesize that a change in the radiogenic strontium (Sr) isotopic ratio (87Sr/86Sr) involved in mineral OC interactions upon changing water saturation conditions implies a destabilization of the mineral OC interaction. We quantified mineral OC interactions using selective extractions in soils facing gradual thaw (Eight Mile Lake, AK, USA) and in sediments with a thawing history of abrupt thaw (Duvanny Yar, Russia), and we measured the 87Sr/86Sr ratio of the selective extracts targeting the Sr associated to mineral OC interactions. Firstly, for water saturated layers with a higher proportion of mineral OC interactions, we found a difference in the 87Sr/86Sr ratio relative to the surrounding layers, and this supports the preservation of a Sr “stable” pool in these mineral OC interactions. We estimated that a portion of these mineral OC interactions have remained undissociated since their formation (between 4% and 64% by Sr isotope mass balance). Secondly, we found no difference in 87Sr/86Sr ratio between layers accumulating Fe oxides at redox interfaces regularly affected by water table changes (or upon thermokarst processes) relative to surrounding layers. This supports the dominance of a Sr “labile” pool inherited from processes of dissolution and precipitation of the mineral OC interactions. Thirdly, our estimations based on a Sr isotope mass balance support that, as a consequence of permafrost thaw, a larger proportion of Sr from primary mineral weathering (>80%) controls the Sr in mineral OC interactions in the saturated zone of deeply thawed soils relative to poorly thawed soils (∼50%). In conclusion, we found that the radiogenic Sr isotope method, applied for the first time in this context, is promising to trace dissolution-precipitation processes of mineral OC interaction in thawing permafrost.