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The upper Homerian Mulde Event was an extinction event that devastated graptolite diversity and occurred before and during the onset of a major perturbation to the global carbon cycle, which is recorded as a double-peaked positive carbon isotope excursion (CIE). Whereas the Mulde Extinction and associated CIE are well documented globally, changes in global sea level associated with the Mulde Event have only been investigated in detail in the West Midlands, England, and Gotland, Sweden. A critical step toward understanding both the drivers and results of global climatic change during the Mulde Event is to constrain changes in eustasy. This study integrates carbon isotope chemostratigraphy and conodont biostratigraphy of Homerian strata in Tennessee, Indiana, and Ohio in an effort to determine if a global sequence boundary is recorded within the ascending limb of the Mulde CIE and to produce a high-resolution chronostratigraphic framework for Homerian strata in the midcontinent United States. Six sections, two from each state, were measured and described. Five were sampled for carbon isotope chemostratigraphy, and one was sampled for conodont biostratigraphy. All sections from Tennessee and Indiana evidently contain the Mulde CIE, whereas the sections from Ohio are less clear due to the truncation of upper Homerian strata. These data demonstrate that a sequence boundary identified herein in Indiana and Tennessee is the same sequence boundary that formed during the ascending limb of the Mulde Excursion in the West Midlands and Gotland.