Fluid pressures too low to be in equilibrium with the topography of the land surface occur in Cretaceous sediments over much of the western Canada sedimentary basin. We used a numerical model to study the origin of low pressure in southern Alberta and its effects on patterns of regional groundwater flow over the past 5 million years. The model accounts for changes in basin topography, conduction and advection of heat, cooling of pore fluid, and rebound of pore volume during erosion. Results show that the ∼3 MPa of underpressuring observed in this region could have formed because the pore volume of sediments expanded slightly as Pliocene-Pleistocene erosion removed some of the confining load. Our calculations provide an estimate for the upper limit for the permeability of Cretaceous shales on a regional scale because results match observed pressures only if we assign vertical permeabilities less than 3 × 10−20 m2 to these sediments. Pore fluid cooled and contracted as erosion reduced the burial depth of the sediments, but this effect could not have played a significant role in generating low pressure unless Cretaceous shales in southern Alberta are extremely stiff (pore compressibilities of the order of 6 × 10−10 Pa−1) and have regional permeabilities of about 10−22 m2. In our simulations, erosion generates potential gradients that drive groundwater along deep aquifers toward regions of lowest pressure in adjacent aquitards. Groundwater, however, moves too slowly to transport a significant amount of heat. The observed west-to-east increase in the geothermal gradient across the study area most likely occurs because sediments that were deeply buried in the west are more compacted and hence more thermally conductive than those in the east.