The character and relative stratigraphic position of paleoclimatic indicators within Upper Mississippian strata of southern West Virginia suggest a link between eustasy and patterns of continental- to global-scale atmospheric circulation. At the cyclothem scale, annual rhythms in marine facies, and paleovertisols and lacustrine carbonates in terrestrial units indicate that seasonal, semiarid climatic conditions prevailed during highstand progradation. In contrast, leached paleosols and coals that underlie sequence boundaries and occur within transgressive heterolithic facies are suggestive of humid climatic conditions during late highstand through early transgression. Milankovitch-band, glacial-interglacial cyclicity may explain both sequence development and the evidence for Late Mississippian climate fluctuations in the Appalachian basin. Shifts from seasonal to humid climatic conditions are attributed to systematic variation in monsoonal circulation, whereby seasonal moisture became restricted to the equatorial belt during the lowstands of each ∼400 k.y. glacial-interglacial cycle.