We estimate density and P‐wave velocity perturbations in the mantle beneath the southeastern South America plate from geoid anomalies and P‐wave traveltime residuals to constrain the structure of the lithosphere underneath the Paraná Magmatic Province (PMP) and conterminous geological provinces. Our analysis shows a consistent correlation between density and velocity anomalies. The P‐wave speed and density are 1% and 15 kg/m3 lower, respectively, in the upper mantle under the Late Cretaceous to Cenozoic alkaline provinces, except beneath the Goiás Alkaline Province (GAP), where density (+20 kg/m3) and velocity (+0.5%) are relatively high. Underneath the PMP, the density is higher by about 50 kg/m3 in the north and 25 kg/m3 in the south, to a depth of 250 − 300 km. These values correlate with high‐velocity perturbations of +0.5% and +0.3%, respectively. Profiles of density perturbation versus depth in the upper mantle are different for the PMP and the adjacent Archean São Francisco (SFC) and Amazonian (AC) cratons. The Paleoproterozoic PMP basement has a high‐density root. The density is relatively low in the SFC and AC lithospheres. A reduction of density is a typical characteristic of chemically depleted Archean cratons. A more fertile Proterozoic and Phanerozoic subcontinental lithospheric mantle has a higher density, as deduced from density estimates of mantle xenoliths of different ages and composition. In conjunction with Re‐Os isotopic studies of the PMP basalts, chemical and isotopic analyses of peridodite xenoliths from the GAP in the northern PMP, and electromagnetic induction experiments of the PMP lithosphere, our density and P‐wave speed models suggest that the densification of the PMP lithosphere and flood basalt generation are related to mantle refertilization. Metasomatic refertilization resulted from the introduction of asthenospheric components from the mantle wedge above Proterozoic subduction zones, which surrounded the Paraná lithosphere. The high‐density PMP lithosphere is presently gravitationally unstable and prone to delamination.