The carbon isotope record from ancient epicontinental seas may contain much more of a local-scale carbon cycling signal than is generally appreciated. A unique opportunity exists to examine this issue in the case of the Late Ordovician Mohawkian Sea of eastern Laurentia, where the Millbrig K-bentonite stratigraphic framework has been used to delineate a time slice at 454 Ma, extending over ~ 1,500,000 km2 of the eastern United States. Across the time slice, carbonate and organic carbon δ13C vary by 4.5‰ and 7.5‰ respectively, a spatial variation that is as large as temporal (secular) changes in epeiric-sea δ13C that have been reported in the past. These new data are considered in the context of geographic variations in lithological, biological, and other geochemical sediment characteristics. Collectively, these sediment properties distinguish regions of the Mohawkian Sea which likely differed in terms of the nature and relative importance of carbon cycling processes. Water-column depth and structure, and barriers to free exchange of water across the Mohawkian Sea, may have been overarching factors in the development of these regions, raising the possibility that changes in circulation patterns, such as those caused by sea-level change, played a role in driving secular carbon isotope excursions by changing the rate of exchange of dissolved inorganic carbon between water masses. If the observed effects of local carbon cycling on the distribution of Mohawkian Sea δ13C were commonplace in ancient epicontinental marine environments, it would imply that local-scale carbon cycling may have left a nontrivial imprint on epeiric-sea records of secular variations in δ13C, in addition to the imprint left by changes in the global carbon cycle. This may have contributed to the broad scatter in δ13C values observed in the Paleozoic portion of the global carbon isotope secular curve.