Major- and trace-element data together with Nd and Sr isotopic compositions and 40Ar/39Ar age determinations were obtained for Late Cretaceous and younger volcanic rocks from north-central Colorado, USA, in the Southern Rocky Mountains to assess the sources of mantle-derived melts in a region underlain by thick (≥150 km) continental lithosphere. Trachybasalt to trachyandesite lava flows and volcanic cobbles of the Upper Cretaceous Windy Gap Volcanic Member of the Middle Park Formation have low εNd(t) values from −3.4 to −13, 87Sr/86Sr(t) from ~0.705 to ~0.707, high large ion lithophile element/high field strength element ratios, and low Ta/Th (≤0.2) values. These characteristics are consistent with the production of mafic melts during the Late Cretaceous to early Cenozoic Laramide orogeny through flux melting of asthenosphere above shallowly subducting and dehydrating oceanic lithosphere of the Farallon plate, followed by the interaction of these melts with preexisting, low εNd(t), continental lithospheric mantle during ascent. This scenario requires that asthenospheric melting occurred beneath continental lithosphere as thick as 200 km, in accordance with mantle xenoliths entrained in localized Devonian-age kimberlites. Such depths are consistent with the abundances of heavy rare earth elements (Yb, Sc) in the Laramide volcanic rocks, which require parental melts derived from garnet-bearing mantle source rocks. New 40Ar/39Ar ages from the Rabbit Ears and Elkhead Mountains volcanic fields confirm that mafic magmatism was reestablished in this region ca. 28 Ma after a hiatus of over 30 m.y. and that the locus of volcanism migrated to the west through time. These rocks have εNd(t) and 87Sr/86Sr(t) values equivalent to their older counterparts (−3.5 to −13 and 0.7038–0.7060, respectively), but they have higher average chondrite-normalized La/Yb values (~22 vs. ~10), and, for the Rabbit Ears volcanic field, higher and more variable Ta/Th values (0.29–0.43). The latter are general characteristics of all other post– 40 Ma volcanic rocks in north-central Colorado for which literature data are available. Transitions from low to intermediate Ta/Th mafic volcanism occurred diachronously across southwest North America and are interpreted to have been a consequence of melting of continental lithospheric mantle previously metasomatized by aqueous fluids derived from the underthrusted Farallon plate. Melting occurred as remnants of the Farallon plate were removed and the continental lithospheric mantle was conductively heated by upwelling asthenosphere. A similar model can be applied to post–40 Ma magmatism in north-central Colorado, with periodic, east to west, removal of stranded remnants of the Farallon plate from the base of the continental lithospheric mantle accounting for the production, and western migration, of volcanism. The estimated depth of the lithosphere-asthenosphere boundary in north-central Colorado (~150 km) indicates that the lithosphere remains too thick to allow widespread melting of upwelling asthenosphere even after lithospheric thinning in the Cenozoic. The preservation of thick continental lithospheric mantle may account for the absence of oceanic-island basalt–like basaltic volcanism (high Ta/Th values of ~1 and εNd[t] > 0), in contrast to areas of southwest North America that experienced larger-magnitude extension and lithosphere thinning, where oceanic-island basalt–like late Cenozoic basalts are common.