The well-exposed Middle Devonian rocks of the Appalachian foreland basin (Onondaga Formation; Hamilton Group, Tully Formation, and the Genesee Group of New York State) preserve one of the most detailed records of high-order sea-level oscillation cycles for this time period in the world. Detailed examination of coeval units in distal areas of the Appalachian Basin, as well as portions of the Michigan and Illinois basins, has revealed that the pattern of high-order sea-level oscillations documented in the New York–Pennsylvania section can be positively identified in all areas of eastern North America where coeval units are preserved. The persistence of the pattern of high-order sea-level cycles across such a wide geographic area suggests that these cycles are allocyclic in nature with primary control on deposition being eustatic sea-level oscillation, as opposed to autocylic controls, such as sediment supply, which would be more local in their manifestation. There is strong evidence from studies of cyclicity and spectral analysis that these cycles are also related to Milankovitch orbital variations, with the short and long-term eccentricity cycles (100 kyr and 405 kyr) being the dominant oscillations in many settings. Relative sea-level oscillations of tens of meters are likely and raise considerable issues about the driving mechanism, given that the Middle Devonian appears to record a greenhouse phase of Phanerozoic history. These new correlations lend strong support to a revised high-resolution sea-level oscillation curve for the Middle Devonian for the eastern portion of North America. Recognized third-order sequences are: Eif-1 lower Onondaga Formation, Eif-2: upper Onondaga and Union Springs formations; Eif–Giv: Oatka Creek Formation; Giv-1: Skaneateles, Giv-2: Ludlowville, Giv-3: lower Moscow, Giv-4: upper Moscow–lower Tully, and Giv-5: middle Tully–Geneseo formations. Thus, in contrast with the widely cited eustatic curve of Johnson et al. (1985), which recognizes just one major transgressive–regressive (T–R) cycle in the early–mid Givetian (If) prior to the major late Givetian Taghanic unconformity (IIa, upper Tully–Geneseo Shale), we recognize four T–R cycles: If (restricted), Ig, Ih, and Ii. We surmise that third-order sequences record eustatic sea-level fluctuations of tens of meters with periodicities of 0.8–2 myr, while their medial-scale (fourth-order) subdivisions record lesser variations primarily of 405 kyr duration (long-term eccentricity). This high-resolution record of sea-level change provides strong evidence for high-order eustatic cycles with probable Milankovitch periodicities, despite the fact that no direct evidence for Middle Devonian glacial sediments has been found to date.