New rhynchonelliformean brachiopods are documented from Upper Cambrian and Tremadoc beds of the Cordillera Oriental and Puna regions, which are representative of the initial radiation of Plectorthoidea on the Andean (South American) shelves of Gondwana. Protorthisina n. gen., so far the oldest known representative of the family Euorthisinidae, and Lesserorthis n. gen. (Euorthisinidae?) are described, as well as the new species Euorthisina? nazarenensis, Kvania mergli, Kvania lariensis, Kvania azulpampensis (with two subspecies), Kvania? primigenia, and Nanorthis calderensis (with two subspecies). Protorthisina, Kvania, and Nanorthis form a stratigraphically continuous series of species displaying well-defined evolutionary trends involving size, shell ornament, and internal features. In the cardinalia, a transition from a V-shaped septalium (typical of Protorthisina) through almost parallel brachiophore plates (typical of Kvania) to the orthoid notothyrial platform of Nanorthis is documented. The species Nanorthis purmamarcaensis Benedetto and “Nanorthis” grandis (Harrington) are considered as the end members of the lineage. The heterochronic (peramorphic) origin of this trend is supported by ontogenetic evidence from species of Kvania and Nanorthis calderensis. The origin of the ‘plectorthoid’ cardinalia of Kvania from a euorthisinid configuration present in the stem group, followed by the appearance of a orthoidlike configuration in Nanorthis, pose an intricate systematic problem. The preliminary phylogenetic analysis of the northwestern basin taxa shows that the Upper Cambrian Protorthisina simplex n. gen. and sp. is the stem group of both the nanorthid and euorthisinid clades. On the basis of the new evidence, the genus Nanorthis is removed from the Orthoidea to the Plectorthoidea, and the diagnosis of the families Euorthisinidae and Nanorthidae are revised.