Megaraptorans are medium- to large-bodied tetanuran theropod dinosaurs known from Cretaceous deposits in Asia, Australia, and especially South America. The megaraptoran skeleton is far from well known, and the humerus is one of the least-frequently preserved elements. Here we describe the first-documented adult humerus of a South American megaraptoran, recovered from the Upper Cretaceous (Turonian–Coniacian) Portezuelo Formation of the Neuquén Basin on the southeast coast of Lago Barreales in Neuquén Province, northern Patagonia, Argentina. The humerus is referred to the namesake megaraptoran Megaraptor namunhuaiquii Novas, 1998, based on its geographic and stratigraphic provenance as well as its morphological similarity to the corresponding element of a juvenile skeleton of the same taxon. Nevertheless, the new adult humerus exhibits osteological distinctions from that of the juvenile that we interpret as reflective of their differing ontogenetic stages. We also highlight anatomical differences between the humerus of M. namunhuaiquii and that of the enigmatic Patagonian theropod Gualicho shinyae Apesteguía et al., 2016, that show that these taxa are not closely related.