Uncertainty persists over whether repetitive stratal rhythms in the Pennsylvanian of Euramerica (so-called “cyclothems”) were externally forced, in all likelihood by waxing and waning of glacial ice centers on Gondwana, or were controlled by autogenic processes. A key to resolving this dispute is the lateral extent of the individual cyclothems, with broad regional extent (beyond the plausible breadth and length of individual depositional systems such as deltas) arguing in favor of an external forcing control. This study provides a sedimentological and sequence stratigraphic analysis of the middle Pennsylvanian (Desmoinesian to early Missourian in North American stratigraphic terminology, Moscovian to early Kasimovian in the terms of the global stratigraphic nomenclature) succession of the southern Illinois Basin in Illinois, Indiana, and Kentucky, eastern USA. An array of eleven lithofacies is recognized, recording deposition of clastic, humic organic, and bioclastic carbonate sediments on a broad, low-gradient, low-paleolatitude shelf and coastal plain that were undersupplied by sediment. These facies are arranged into thirteen repetitive vertical cycles (sequences), each of which can be traced across the entire basin west to east (perpendicular to the paleoslope direction) across a distance of 250 km. Sequences are bounded by erosion surfaces that define 1–4 km-wide, deeply incised valley-fills (IVFs) that are mostly elongate towards the south-southwest, the dominant direction of paleoflow. In the west–east direction, valley erosion surfaces pass laterally into well-developed paleosols, incised locally by smaller channels. Each of these surfaces is laterally persistent across the basin. IVFs comprise multi-story bodies of conglomerate–breccia and sandstone, passing upward into heterolithic sandstone–mudrock associations, recording fluvial and later estuarine environments. Coal bodies typically occur at the tops of IVFs and are interbedded with heterolithic facies recording tidal influence, indicative of initial flooding by the sea. They are in turn overlain by estuarine and marine mudrocks and bioclastic carbonates, recording the maximum extent of marine flooding in a cycle. Each sequence is completed by heterolithic to sandstone-dominated facies of deltaic aspect that are typically truncated by the next erosion surface (sequence boundary). Plausible modern analogs suggest that sea-level excursions were of the order of 20–40 m. The great lateral persistence of not only the thirteen sequences, but also many of their component beds, argues strongly for an external control on sediment accumulation. Eccentricity-paced glacial cycles in Gondwana are invoked as the most likely cause of the cyclicity. The low-accommodation context of the Illinois Basin (average accumulation rate 6 cm/ky) contributed to the incomplete, condensed, and strongly top-truncated nature of preserved sequences.