Using commercial hydrofracture data to supplement published stress data, we map regional variations in least horizontal stress magnitude (Sh) and orientation within the Paleozoic sediments of the Appalachian Plateau. Systematic trends revealed by the data are examined for correlations with structure (the study area includes a prominent salt detachment) and tectonic history. The dominant stress component present at all depths (including basement) throughout the region is ENE oriented compression and is most likely of tectonic origin. No deviations from this rule are found that are statistically significant. Near‐surface (<600 m) stresses are consistently greater than the overburden with “strike‐slip” regime conditions prevailing below. However, where the Salina salt beds are present, “thrust” regime conditions extend deeper, reaching the salt in most places where data are available (limited to where the salt is shallower than 1.5 km). At the salt, a discontinuity in the trend of Sh with depth marks the abrupt transition to the underlying strike‐slip regime characterized by least stress ratios (i.e., Rh = Sh/Sv) in the range 0.5–0.7 and extending to basement. The comparatively high stress found above the salt may reflect a difference between the strain histories of the overlying and underlying sections facilitated by mechanical decoupling by the salt and perhaps includes a component of stress remnant from NW oriented Alleghanian shortening of the upper section. The lower (subsalt) stress regime extends beyond the eastern salt margin and displays remarkable uniformity over distances of hundreds of kilometers. This is particularly evident across Ohio, where an Rh value of 0.6±0.05 appears valid down to basement. North of Ohio, values increase markedly, whereas to the south of the salt pinch‐out, in West Virginia and eastern Kentucky, values as low as 0.35 are found in Devonian shales at 1–1.5 km depth, although values deeper in the section may be higher. The northward increasing trend can be reasonably well modeled as the effect of persisting lithospheric flexure due to the Pleistocene ice sheet. However, flexure was much greater in the past, and as Devonian shales in south Ohio/West Virginia are currently only marginally stable, a modest increase over the present flexure would be expected to cause shear failure. This suggests that the very low stress in the shales of south Ohio/West Virginia is of different origin and more recent than the Pleistocene.