Marine dissolved organic matter (DOM) is one of the most important carbon stocks for regulating the global climate, yet the mechanisms responsible for their long-term persistence remain unclear. Here we uncover a universal mechanism sustaining this carbon stock based on DOM's thermodynamic properties. By integrating molecular-level analyses of DOM's thermodynamic favorability in controlled incubations with pan-ocean surveys, we demonstrate that microbial processing drives DOM toward thermodynamic equilibrium. Carboxyl-rich alicyclic molecules, a widely used proxy of persistent DOM, exemplify near-equilibrium with ratios of production to consumption approaching unity. This shift to equilibrium is further observed along vertical (from surface to deep ocean) and horizontal (from North Atlantic to North Pacific Ocean) DOM transport, consistent with microbial processes that minimize Gibbs free energy. These processes reconcile DOM's dynamic turnover with its millennial-scale stability, establishing thermodynamic constrains as the linchpin of marine DOM persistence and as a principle to redefine models of the global carbon cycle.