Although the majority of young volcanic rocks in island arcs typically have 238U excesses, continental arc rocks display both 238U and 230Th excesses. In fact, there is a global correlation between the sense of U-series disequilibria and crustal thickness that suggests that crustal thickness may somehow influence the processes that fractionate U from Th. At Cotopaxi Volcano, Ecuador, (238U) / (230Th) values of 1.03-1.14 in rhyolites are attributed to accessory phase fractionation, whereas (238U) / (230Th) values of 0.96-1.07 in andesites can be explained by several potential processes, including melting of garnet-bearing lower crust. The Cotopaxi rocks have non-fractionated HFSE ratios and La / Yb values that are consistent with melting of a garnet-bearing lithology, and we suggest a model of lower crustal melting and assimilation to account for the range of U-series data in the Cotopaxi andesites. Mantle like 87Sr / 86Sr and 143Nd / 144Nd values indicate that the assimilant was a relatively juvenile and/or mafic component. The rhyolites contain apatite and allanite, fractionation of which can generate 238U excesses during crystallization, and modeling shows that 70-90% crystallization of an assemblage containing these phases could generate the observed 238U excesses. These data suggest that multi-level AFC processes contribute to magma evolution at Cotopaxi Volcano as magma traverses the continental crust of the Northern Volcanic Zone. On the basis of the 238U-230Th-226Ra data, the time for assimilation and ascent of the andesites was < 8000 yr, whereas the rhyolites may have resided in the crust for 70-100 ky. The modification of U-Th isotopic signatures may be a common feature of differentiated magmas in continental arc settings and such potential effects should be considered along with interpretations involving variable mantle sources and melting regimes.