Spatial variation in the environment can lead to divergent selection between populations occupying different parts of a species’ range, and ultimately lead to population divergence. The colonization of new areas can thus facilitate divergence in beneficial traits, yet with little differentiation at neutral genetic markers. We investigated genetic and phenotypic patterns of divergence between low- and high-altitude populations of cinnamon teal inhabiting normoxic and hypoxic regions in the Andes and adjacent lowlands of South America. Cinnamon teal showed strong divergence in body size (PC1; PST= 0.56) and exhibited significant frequency differences in a single nonsynonymous α-hemoglobin amino acid polymorphism (Asn/Ser-α9; FST= 0.60) between environmental extremes, despite considerable admixture of mtDNA and intron loci (FST= 0.004–0.168). Inferences of strong population segregation were further supported by the observation of few mismatched individuals in either environmental extreme. Coalescent analyses indicated that the highlands were most likely colonized from lowland regions but following divergence, gene flow has been asymmetric from the highlands into the lowlands. Multiple selection pressures associated with high-altitude habitats, including cold and hypoxia, have likely shaped morphological and genetic divergence within South American cinnamon teal populations.