Marginal oceans have unique ventilation and circulation patterns compared to the open ocean interior, but the consequences of these processes for regional carbon cycling remains insufficiently characterized. The South China Sea (SCS), the largest marginal sea of the North Pacific Ocean, features a distinctive three-layer circulation that links surface, intermediate and deep waters. Here, we investigated DOM molecular composition across the northern, central and southern SCS, encompassing the three circulation layers, using ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Molecular analyses revealed broad compositional similarity across the entire SCS (>80% Bray–Curtis similarity) and was likely shaped by the combined influence of water mass circulation and microbial transformation, as indicated by redundancy analysis. In contrast, the central SCS displays divergent DOM molecular composition and characteristics, potentially primarily influenced by the basin-scale hydrodynamic circulation. Across all sites, a relatively small fraction of molecules accounted for most FT-ICR MS signal intensity, and certain formula groups (CHO and CHONS) preferentially accumulated whereas others (CHON and CHOS) were selectively removed, consistent with observations from other ocean regions. These patterns support the structurally recalcitrant hypothesis as a key mechanism underlying the persistence of oceanic refractory DOM pool. By elucidating DOM molecular composition in the SCS, this study provides molecular-level insights into the processes shaping regional biogeochemical cycles and carbon sequestration in marine ecosystems.