Late Cenozoic opening of the Fram Strait led to formation of the NW-SE striking, eastern North Greenland oblique-shear margin at transition from the Norwegian-Greenland Sea to the SW Eurasia Basin. Onshore geology exposed on large peninsulas in front of the major Greenland Inland Ice reveals a highly complex, Paleozoic-early Cenozoic pre-opening setting. However, due to extreme ice conditions, very little is known about the offshore areas seawards of - and between - the peninsulas. Consequently, prevailing structural-tectonic models of the margin tend to be significantly oversimplified and inadequate. We present the first, combined onshore-offshore, model of the margin integrating onshore outcrops with potential field data, new offshore seismic reflection data and receiver-function analysis of seismic broad band data. The results reveal a margin which is far more complex than previously anticipated. In particular, we interpret strong margin segmentation along N/NE-striking fault structures. The structures are likely to have formed by Late Mesozoic-early Cenozoic strike-slip tectonics and have continued to be active during the late Cenozoic. A more than 8. km deep sedimentary basin is interpreted to underlie the central Wandel Sea, confined by these N/NE-striking structures. We suggest that similar margin segmentation affected the conjugate Yermak Plateau-North Svalbard margin as well as parts of the NE Greenland margin to the SE. Hence, the results have important implications for the general understanding of the Mesozoic-early Cenozoic development of the intra-continental De Geer Mega-shear Region between North Greenland and Eurasia. © 2009 Elsevier B.V.