This study aims to investigate the effects of parent rock and minerals on lateritic weathering. The study presents X-ray diffraction (XRD), whole-rock geochemistry, and Nd-Sr isotopic data for examining two profiles, 10 and 12 m thick, respectively, that illustrate the regional tropical weathering status in the Midwest of Brazil. The profiles, developed from metasedimentary and sedimentary rocks, are constituted by saprolite, mottled horizon, lateritic duricrust, and oxisol. Across the profiles, the minerals controlling the weathering geochemistry are muscovite, microcline, quartz, kaolinite, hematite, goethite, and gibbsite. Red and yellow zones in the saprolite and mottled horizon as well as the lateritic duricrust with breccia/fragmental, pisolitic, and oolitic textures make profile 1 more complex. In contrast, profile 2 has an oxisol that mantles the homogeneous vermiform lateritic duricrust. Fe2O3, accumulated during surface weathering, is a potent element in the geochemical profile control since it forms the harder goethite to hematite lateritic duricrust, bearing most of the trace elements (As, Cu, Cs, Pb, Sc, Sr, Th, U, V, and Zn) with similar ionic radii and electrovalence. The LREE have affinity for the elements of the Fe2O3 group of the lateritic duricrust. On the other hand, the K2O group together with Zr and TiO2 e in the phyllite, saprolite, and mottled horizon of profile 1, are associated with the HREE. Additionally, in profile 2, the HREE are mostly associated with the Al2O3 group and the residual minerals in the oxisol. The indication that REE is associated with phosphates, zircon, rutile/anatase, cereanite, and muscovite/illite, which have variable weathering behavior, caused the REE fractionation to occur across and between the profiles. Despite the REE fractionation, the ƐNd(0) values along the profiles consistently maintain the signature of the parent rock. Muscovite and microcline weathering, in profiles 1 and 2, respectively, control the decrease in 87Sr/86Sr signatures of both profiles and the distinct radiogenic ratios. The development of lateritic duricrust in both profiles indicates a similar weathering intensity, although the gibbsite–kaolinite predominance in the oxisol of profile 2 highlights a geochemical reorganization under humid conditions, as well as near-intense soluble silica leaching.