Topographic features of the sub-Athabasca unconformity surface, such as paleovalleys, topographic highs, and fault scarps, have been documented locally in the eastern Athabasca Basin, and available data indicate that they are spatially associated with mineralization. However, the mechanisms by which such topographic features were generated, their size and distribution at the regional scale, as well as their relationship to mineralization, are still not completely understood. A 100 by 60 square kilometre area of the southeastern Athabasca Basin, encompassing the McArthur River, Phoenix, and Key Lake deposits, was selected to study the relationship between these topographic features and U mineralization. In this region three dominant sets of sub-vertical faults were identified on the basis of aeromagnetic data: northeast-trending, north–northwest-trending, and northwest-trending. A detailed three-dimensional (3-D) model of this part of the basin was constructed using data from more than 1200 drill holes. This model reveals numerous dominantly northeast-trending ridges and valleys in the unconformity surface. Among these, a prominent northeast-trending ridge is situated close to the McArthur River – Key Lake deposits trend. Structural interpretation and cross-sections illustrate that the topographic features that have been documented in previous studies are a function of three principal factors: (i) pre-Athabasca group ductile-brittle faulting and alteration; (ii) differential weathering and erosion; and (iii) syn- to post-Athabasca ductile-brittle reactivation of pre-existing graphite-rich ductile shear zones. The topographic features and associated faults may have acted as conduits and barriers to fluid flow and thus controlled alteration patterns and uranium mineralization.