The genus Amaranthus (pigweeds) is a group of ∼74 monoecious or dioecious annual species native to every continent but Antarctica, frequently associated with natural and human disturbance, with several economically important domesticated and weedy species. We set out to reconstruct the phylogeny of Amaranthus, with broad geographic sampling, in order to answer questions about biogeographic relationships in the genus and the monophyly of the subgenera. Fifty-eight species were included inmaximum parsimony and Bayesian phylogenetic analyses based on ITS and three low-copy nuclear genes (A36, G3PDH, and Waxy), as well as two chloroplast regions (trnL5′-trnL3′ and matK/trnK). Topology tests were also employed to test taxonomic hypotheses about incongruence between trees and the monophyly of clades containing Galápagos species. Our analyses support the origin of the genus in the Americas, with a single long-distance dispersal event to the Old World, and both nuclear and chloroplast trees recover three to fourmajor clades, roughly corresponding to three subgenera recognized based on morphology. However, there are species in all of these clades that were not predicted based on morphology, and we discover previously unsuspected relationships between Galápagos species and species from the North American Southwest, which comprise small monophyletic groups outside of the three recognized subgenera. Additionally, an important herbicide resistant weed species (A. palmeri) and its sister species are placed into different large clades based on nuclear or chloroplast data, suggesting a chloroplast capture event. These results will provide a basis for further exploration of the evolution of weedy ecological strategies in the group.