As indicated by drilling and geophysical data, the Mississippi Valley Graben, the Rough Creek Graben, together with the Rome Trough of eastern Kentucky and West Virginia, are fault-bounded graben structures filled with as much as 27,000 feet of Early to Middle Cambrian sediments. Detailed regional mapping of Cambrian and younger strata within and surrounding these structures indicates that they formed contemporaneously. The proximity of these structures suggests they developed within the same regional stress fields and tectonic environments. These three structures are mechanically and kinematically connected, and formed part of a single continent-scale rift system produced during the breakup of Rodinia and the separation of Laurentia from Amazonia. Data including stratigraphic tops from 1,764 wells, interpretations of 106 seismic profiles, aeromagnetic and gravity survey analysis, and mapped surface geology and structures were used within this project. Seven stratigraphic packages resolvable in both geophysical well logs and reflection seismic profiles were mapped in the subsurface across parts of Kentucky, Ohio, Indiana, Illinois, Missouri, and Tennessee. These stratigraphic units were then analyzed through structure maps, isopachous maps, and across 12 regional well-based cross sections. Detailed analysis of thickness patterns of seven major stratigraphic packages was used to identify the locations and timing of major fault movements within the study area. The regional patterns of fault movements through time were used to investigate how the structures evolved in response to the tectonic episodes in southeastern Laurentia during the Cambrian through Devonian Periods. Active rifting of the Precambrian crystalline bedrock began by the Early Cambrian, and resulted in a thick deposit of Reelfoot Arkose and Eau Claire Formation within the Mississippi Valley and Rough Creek Grabens, and the Rome Formation and Conasauga Group within the Rome Trough. Major tectonic extension ended by the Late Cambrian, prior to the deposition of the Knox Supergroup. Counter-clockwise rotation of the regional sigma-1 stress field between the Middle Ordovician and Early Mississippian (Taconic through Acadian Orogenies) resulted in the reactivation of varying sets of preexisting faults through time. The locations, orientations, and timing of these active faults relate to the deep architecture of the rift system.