Cold-seep deposits are the remnants of ancient chemosynthetic ecosystems that derive energy from microbial anaerobic oxidation of methane (AOM) using seawater sulfate. They provide a physical record of a microbial process that plays a critical role in regulating biospheric methane. Although highly 13C-depleted kerogen suggests that AOM dates back 2.7 b.y., puzzlingly, the oldest reported cold seeps only appear at 635 Ma and lack carbon isotopic signals (<–30‰ Peedee belemnite) that are diagnostic of AOM in examples younger than 350 Ma. Using a one-dimensional biogeochemical reaction-transport model, we confirm that these discrepancies are an expected consequence of changes in seawater chemistry. More specifically, sub-millimolar (mM) to millimolar seawater sulfate concentrations ([SO42–]SW) and elevated concentrations of dissolved inorganic carbon that characterized seawater through much of the Precambrian limited AOM-driven carbonate supersaturation and 13C depletion, making seep carbonates less likely to form and more challenging to identify. Moderate 13C depletions observed in 420–370-m.y.-old cold-seep carbonates (independently identified by fossil assemblages and contextual and textural observations) indicate [SO42–]SW < 5 mM in this interval. This is significant because low [SO42–]SW has been linked to widespread ocean anoxia in the early Paleozoic, an environmental condition thought to have influenced the evolution, extinction, and recovery of early animals.