The deep regolith of the southeastern United States has undergone rapid erosion in the last two centuries due to intensive agricultural practices, which has altered the landscape and its inherent fertility. Parent material, landscape position, and land use are important factors in controlling the mineral and elemental composition of soil profiles. Independent quantitative X-ray diffraction (QXRD) and whole-rock chemical analysis of eight weathering profiles agreed well and allow mineral reaction pathways to be constrained as particles are conveyed in the subsurface. QXRD analysis of saprolite, argillic, and soil A-horizons in the profiles highlights the imprint of bedrock on the regolith, which includes Neoproterozoic meta-tonalitic to meta-granodioritic and Paleozoic meta-granitic to biotite- and amphibolite-gneissic lithologies. Also, aeolian input slightly influenced A-horizon composition. The clay mineral assemblage is dominated by kaolinite, but profiles differ in the amount of interstratified clay minerals, halloysite, hematite, goethite, and gibbsite. Rare-earth element totals vary between 30 and 1048 ppm and are generally correlated positively with clay and clay mineral content. Eu and Ce anomalies reflect parent rocks and subsequent hydrolysis and redox history, with trends depending upon landscape position and clay content in the weathering profile. Weathering profiles on a high-order interfluve and those that were actively cultivated have thick argillic horizons (as defined by clay mineral abundance) and are depleted in alkali and alkaline-earth elements. Profiles proximally developed on old-field pine and never-cultivated hardwood forest land do not show large differences in mineral composition trends, whereas profiles on old-field sites with ongoing cultivation exhibit assemblages enriched in clay minerals and (oxyhydr)oxides. Old-field pine sites that were historically eroded by previous cultivation tend to have shallower and thinner argillic horizons, which may well impact critical-zone processes involving gas and water fluxes. This study highlights that mineral compositions of deep regolith, saprolite, and shallow soil horizons are dependent on local geomorphology (i.e. watershed- and hillshed-orders). Quantifying soil and regolith compositional trends across the landscape is a prerequisite for determining rates of chemical and physical erosion on human and geologic time scales.