The largest reservoir of the powerful greenhouse gas methane is in marine sediments, and catastrophic release of this methane has been invoked to explain climate perturbations throughout Earth history. Marine methane oxidation is mainly coupled anaerobically to microbial sulfate reduction, which both limits and controls the release of methane from this sedimentary reservoir to the rest of Earth’s surface. Methane can be transported within the pore space of marine sediments either via diffusion or as bubbles. When methane travels in bubbles, these bubbles often are not completely oxidized and reach the overlying water where the methane emerges from the sediment in cold seeps. Although paleo–cold seeps can be identified by geological features such as carbonate mounds, a geochemical signature for cold seeps remains elusive. We demonstrate, using the sulfur and oxygen isotope composition of sulfate, that a unique isotopic signature emerges during microbial sulfate reduction coupled to methane oxidation in bubbling cold seeps. This isotope signature differs from that when sulfate is reduced by either organic matter oxidation or by the slower, diffusive flux of methane within marine sediments. We also show, through a comparison with the literature, that this unique isotope fingerprint is preserved in the rock record in authigenic buildups of barite associated with methane cold seeps.