The sedimentary dissolved organic matter (DOM) comprises mainly humic-like compounds, which are regarded as refractory for their molecular complexity and therefore play essential role in long-term oceanic carbon preservation. However, the bio-reactivity of refractory DOM is highly environmental context dependent but poorly explored in sediments, especially the energy-limiting deep-sea sediments. Here, the reaction rate of sedimentary DOM was modeled, and its interaction with microbial communities was studied in 5 sediment cores from the eutrophic Pearl River Estuary (PRE) to the oligotrophic deep-sea basin in the northern South China Sea. Our modeling results showed net production of humic-like DOM in coastal sediments, but net consumption in deep-sea sediments. An increasing number of microbial groups were tightly associated with humic-like DOM from coastal to deep-sea sediments, dominated by the ones harboring the metabolic potential of refractory OM degradation, e.g., Anaerolinaea and Dehalococcoidia. These evidences suggest that humic-like DOM gets degraded by microbes when relatively labile DOM is no longer accessible, especially in the energy-limiting deep-sea environments. Refractory DOM serves as important energy source for subsurface microbial communities which further reduces its inventory and turnover time.