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The later Cambrian Steptoean Positive Carbon Isotope Excursion (SPICE) event was an episode marked by pronounced changes to the global biogeochemical cycles of carbon and sulfur and significant extinctions on several paleocontinents including Laurentia (North America). While the exact cause(s) of these events remains debated, various lines of evidence suggest an increase in the areal extent of anoxia at the seafloor was a likely feature. Here, we explore whether changes in local oxygenation accompanied the onset of the SPICE in southern Laurentia using cores of the Nolichucky and Eau Claire Formations from Ohio and Kentucky, USA, that represent a transect into the Rome Trough/Conasauga intrashelf basin. At our study locations, the initial positive δ13C shift of the SPICE occurs in conjunction with increases in the abundance and δ34S of sedimentary pyrite. Further local redox conditions, tracked using iron speciation analysis, indicate anoxic conditions developed at the two proximal locations after the start of the paired isotopic excursions. However, the location near the basin center shows no indication for anoxia before or during the onset of the SPICE. While this signal may reflect the structure of local redox conditions within the basin, with the development of anoxia limited to the basin margins, we argue that authigenic iron enrichments were muted by sedimentary dilution and/or the enhanced authigenesis of iron‐bearing sheet silicates near the basin center, masking the signal for anoxia there. Regardless of the areal extent of anoxia within the basin, in either scenario the timing of the development of anoxic bottom waters was concurrent with local faunal turnover, features broadly consistent with a global expansion of anoxia playing a role in driving the isotopic trends and extinctions observed during the event. [ABSTRACT FROM AUTHOR]