The tectonic relationship between epeirogenic features, fault-and-fold zones, and topography in the cratonic platform of the United States remains an open question. To address this question, we have plotted a compilation of structural traces (the intersection of Midcontinent fault-and-fold zones with the ground surface) on a DEM of the region. This plot reveals a correlation between these traces and both local-scale and regional-scale topographic features. Specifically, individual traces control stream orientation and align with boundaries of local escarpments. They also underlie a set of subtle, NW-trending ridges, whose shapes represent the surface manifestation of positive flower structures indicative of transpressional deformation. Local pull-apart basins, similarly, are indicative of transtensional deformation. At a regional scale, fault-and-fold zones align with both the NE and SE boundaries of the Ozark Plateau, suggesting that the St. Francois Mountains represent the exhumed corner of a tilted crustal block. Results from the EarthScope OIINK array emphasize that the edge of this crustal block correlates with an up to 7.5 km-high step in the subsurface elevation of the Great Unconformity. It also coincides with a belt of seismicity, a region of low-velocity seismic waves, and a significant drop in Moho depth. The persistence of topography in the Ozark Plateau and of bordering ridges hints that displacements along the boundary between the Illinois Basin and the Ozark Dome, known to be significant during the Paleozoic, are still sufficient to maintain uplift through post-Paleozoic time. Examination of drainages in the plateau indicate that streams display typical graded profiles, but do not have obvious knick points, implying uplift is not rapid or localized enough to generate knick points. Overall, the spatial association of upper-crustal faults, deep-crustal steps, topography, and seismicity, along the boundary of between the Ozark Dome and the Illinois Basin, emphasizes that faulting serves a significant role in the evolution of regional, long-lived epeirogenic features, and that these structures continue to exert a subtle control on topography in post-Paleozoic time.