The most prominent of the two major global δ13C excursions in the Ordovician, the Hirnantian δ13C excursion (HICE), which is previously recorded from the uppermost Ordovician in a few sections in Nevada, Quebec, Arctic Canada, Baltoscandia, Scotland and China, is documented for the first time from the North American Midcontinent. Samples through the Girardeau Limestone and Leemon Formation in Missouri and Illinois show elevated δ13C values of + 4 ‰to + 5 ‰. Although not determined precisely, the beginning of the HICE is likely to be in the upper part of the Orchard Creek Shale, and it ends in the upper Leemon Formation. Being extraordinarily useful chronostratigraphically, the presence of the HICE makes it possible to provide a firm dating of the study interval, whose age has long been controversial. Comparison between the study sections and coeval HICE sequences in North America and Europe show striking similarities, especially in sea-level history, indicating that major local lowstands reflect eustatic sea-level changes. A comparison with Hirnantian diamictite successions in North and South Africa and Argentina suggests that these lowstands correspond to two major Gondwanan glacial episodes.