Early magmatism of the southern Rio Grande rift was strongly controlled by the thermal history of the lithosphere. The compositions of igneous rocks in southern New Mexico record a general shift in magma source regions through the Cenozoic from lithosphere to asthenosphere and from upper crust to lower crust and, finally, to little crustal involvement. Extension began as early as 36 Ma, coincident with the onset of bimodal volcanism of the middle Tertiary ignimbrite flare-up and production of half grabens after a short episode of post-Laramide subduction-related volcanism. Oligocene mafic magmas have incompatible trace element patterns similar to modern continental-arc basalts (low Nb, Ta, and Ti; high Rb/Nb, Ba/Nb, and La/Nb). The most mafic magma has 87Sr/86Sr and ϵNd values near bulk Earth (0.704771 and +0.2, respectively). The Oligocene mafic to intermediate-composition suites evolved toward slightly higher 87Sr/86Sr, lower ϵNd, and nonradiogenic Pb isotopic compositions (87Sr/86Sr = 0.70440–0.70785; ϵNd = −2.2 to −4.8; 206Pb/204Pb = 17.039–18.084, 207Pb/204Pb = 15.387–15.498; 208Pb/204Pb = 37.094–38.130) and are interpreted as partial melts of slightly hydrated lithosphere that were contaminated in the lower crust. Contemporaneous rhyolitic magmas have more radiogenic Sr and Pb isotopic compositions (87Sr/86Sr = 0.7111; ϵNd = −4.5; 206Pb/204Pb = 18.435; 207Pb/204Pb = 15.538; 208Pb/204Pb = 38.607) and record the involvement of an upper-crustal component. Silicic volcanism ceased abruptly at 28.5 Ma, but mafic to intermediate-composition lithospheric magmatism persisted until 24 Ma. Although extension continued, forming half grabens with sedimentary fill, the period between 24 and 10 Ma was amagmatic. This lack of volcanism and the end of lithosphere-dominated magma genesis reflect the effective scavenging of the hydrated parts of the lithospheric mantle by middle Tertiary magmatism, which produced a refractory, infertile, subcontinental lithosphere. Volcanism resumed at 10 Ma with sporadic eruption of tholeiitic and alkalic basalts having trace element patterns similar to oceanic-island basalts (high Nb, Ta, and Ti; low Ba/Nb and La/Nb), depleted Sr and Nd isotopic compositions (87Sr/86Sr = 0.70297–0.70396; ϵNd = +4.7 to +7.3), and more-radiogenic Pb isotopic compositions (206Pb/204Pb = 18.460–19.698; 207Pb/204Pb = 15.461–15.684; 208Pb/204Pb = 38.091–39.411) than the lithosphere-derived suites. The composition of these late Cenozoic basalts records a dramatic shift in source region to upwelling asthenosphere that melted by adiabatic decompression.