The origin of cratonic sheet sandstones of Proterozoic and early Paleozoic age has been a long-standing problem for sedimentologists. Lower Paleozoic strata in the Upper Mississippi Valley are best known for several such sandstone bodies, the regional depositional histories of which are poorly understood. We have combined outcrop and subsurface data from six states to place the Upper Cambrian Wonewoc (Ironton and Galesville) Sandstone in a well-constrained stratigraphic framework across thousands of square kilometers. This framework makes it possible for the first time to construct a regional-scale depositional model that explains the origin of this and other cratonic sheet sandstones.