The late Paleozoic ice age (LPIA) began in the Mississippian period (Visean-Serpukhovian) and is associated with a global mass extinction. This study examines how the development of high-amplitude glacioeustasy at the start of the LPIA affected the taxonomic richness and ecologic diversity of tropical marine macro-invertebrate assemblages from the Illinois Basin (United States). Rarefaction and faunal turnover analyses reveal that regional taxonomic and guild richness persist nearly unchanged across the inferred onset of the LPIA and through multiple glacioeustatic cycles spanning a total duration of ∼3 to 5 myr. In addition, low levels of taxonomic turnover characterize the LPIA transition and subsequent glacioeustatic cycles; 76% to 92% of pre-LPIA taxa persist into the ice age where they account for 63% to 75% of LPIA taxa. Thus, the onset of high-amplitude glacioeustasy was not a main driver of regional biotic change or extinction in the Illinois Basin at the start of the LPIA. Potential mechanisms for the regional persistence of taxonomic diversity and faunal composition despite major glacioeustasy include habitat tracking and an immigration rescue effect, where localized extinction is balanced by immigration of taxa from nearby areas. Finally, evidence from this and other studies of late Paleozoic faunal turnover suggest that persistence, not change, is the normal biotic response to high-amplitude glacioeustasy during the LPIA.