Paleozoic/Mesozoic strata of the United States continental interior contain arrays of steeply dipping faults and associated monoclinal forced folds. Though these Midcontinent fault-and-fold zones clearly were active in pulses during the Phanerozoic, we suggest that they initiated during episodes of Proterozoic extensional tectonism. Based on fault-trace orientation, we divide Midcontinent fault-and-fold zones into two sets—one trending N to NE and the other trending W to NW. These sets effectively break the upper crust into blocks that jostle with respect to each other in response to changes in stress state. Notably, many W- to NW-trending fault-and-fold zones link along strike to define semi-continuous NW-trending deformation corridors. One of these, the 200 km-wide Transamerican tectonic zone (TTZ), traces over 2,500 km from Idaho to South Carolina. Seismic events occur in association with fault-and-fold zones, presumably because the zones persist as crustal weaknesses and/or stress risers. Significantly, seismicity most frequently occurs where N- to NE-trending fault-and-fold zones cross the TTZ, suggesting that intracratonic strain in the United States currently concentrates at or near intersecting fault zones within this corridor.