Analysis of electric and geologic logs of 517 shallow wells (91 m, 300 ft deep) in southeastern Missouri has revealed a subsurface structural high (herein called the Charleston Uplift) trending N46°E from near New Madrid, Missouri, to Cairo, Illinois, that juxtaposes Paleocene Flour Island Formation against Eocene Claiborne Group. The Charleston Uplift is 30 km (19 miles) long, 7.2 km (4.5 miles) wide, and has a relief of 36 m (120 ft) at the unconformity surface between the Paleogene and Quaternary sections. Two seismic‐reflection soundings, one conducted north of the uplift, and the second conducted within the uplift indicate 60 m (198 ft) of apparent structural relief on the underlying top of the Paleozoic, 47 m (155 ft) on the top of the Late Cretaceous, and 19 m (63 ft) on a Tertiary reflector. The Charleston Uplift is interpreted to be the northeastern extension of the New Madrid North fault of the New Madrid seismic zone and locally the western margin fault zone of the Reelfoot rift. Although no surface faulting has been mapped along the Charleston Uplift, the uplift appears to have influenced the Holocene course of the Mississippi River and displaced the Paleocene/Quaternary unconformity, thus indicating Quaternary displacement of the Charleston Uplift across southeastern Missouri, which may continue beneath the Ohio River valley into adjacent Illinois and Kentucky. Thus, the Charleston Uplift strongly suggests Quaternary structural continuity between the Reelfoot rift and Rough Creek graben of Kentucky. Although currently seismically quiet, the 12 February 2012 M 3.9 earthquake and probably the 31 October 1895 ∼M 6.6 Charleston earthquake occurred on this structure, thereby illustrating the seismic potential of this structure and extending the New Madrid North fault system at least 30 km (19 miles).