An exceptionally complete and extensive new exposure of the Catskill Formation (Upper Devonian) in the Susquehanna Valley of central Pennsylvania demonstrates that fluctuations of relative sea level of at least two orders in the Milankovitch range affected its depositional history well into the Famennian Stage. Seven incised-valley-fill (IVF) units, ranging in thickness from 10 to 33 m, are present up to about 600 m above the base of the Sherman Creek Member. Where fully developed, they have the three-part vertical sequence recently proposed as the signature of IVFs: (1) above a basal scour surface, cross-stratified sandstone and conglomerate deposited in environments that were initially high-intensity braided fluvial but that became increasingly affected by marine storm processes; (2) a medial unit of green-gray fissile mudrock containing symmetrical sandstone ripples in flaser and linsen forms accumulated in the anoxic calm of the central zone of an estuary; and (3) an upper unit of wave-rippled sandstone and/or channelform sandstone representing progradational bayhead filling of the estuary. Other marine influences on deposition of the Sherman Creek Member are indicated by a diverse suite of brachiopods and by wave-rippled sandstone. A rough estimate suggests that these marine incursions into the Catskill coastal-alluvial plain represent fourth-order fluctuations of relative sea level. Features of the Irish Valley Member confirm that deposition of fissile mudrock took place on the marine shelf under low-energy, anoxic conditions only intermittently interrupted by storms, and that thicker (>2 m) sandstone units represent sharp-based shelf sand bars. Fifth-order fluctuations of relative sea level produced numerous, repetitious shallowing-upward sequences in both paralic and shelf facies of the Irish Valley. These interpretations provide the basis for sequence-stratigraphic analysis of both members of the Catskill Formation as a unified depositional system. In lowstand phases, Catskill streams erosionally incised their courses into the coastal-alluvial plain, bypassing coarser sediment to the shelf, where it accumulated as lowstand shelf fans. In the transgressive phase, incised valleys were drowned as transgressive surfaces moved diachronously upvalley, changing braided fluvial systems to storm-wave-influenced marginal-marine sand environments, followed by the establishment of anoxic, deeper estuarine conditions. On the shelf, transgressions restored muddy conditions of low-energy and anoxia. Highstand conditions resulted in filling of the incised valley by aggradation in the estuary and progradation at the bayhead, gradually returning the area to pre-incision coastal-alluvial plain conditions.