The new Chaetostoma-group genera Andeancistrus and Transancistrus are described based on recently collected material from rivers draining the respective Amazonian and Pacific slopes of the Andes Mountains in Ecuador. Andeancistrus is diagnosable from all other members of the Chaetostoma group by having a fully plated snout, lacking cheek odontodes that extend past the opercular flap, and by having eight vs. nine branched dorsal-fin rays. The new species Andeancistrus eschwartzae is also described and diagnosed from its only congener (A. platycephalus) by having a black to dark gray base color of head and body (vs. light gray), irregularly shaped round to vermiculate yellow-gold spots smaller than half naris diameter evenly distributed across head, lateral and dorsal surfaces of the body and fin rays (vs. white to blue uniformly round spots), and by lacking enlarged clusters of odontodes at the posteromedial apex of most lateral body plates (vs. odontode clusters present). Transancistrus contains the species T. aequinoctialis and T. santarosensis, which can together be diagnosed from all other members of the Chaetostoma group except Chaetostoma by lacking plates along the anterior and lateral margins of the snout; they can be diagnosed from Chaetostoma by having a much narrower unplated snout region, approximately as wide as the maximum diameter of the orbit (vs. twice this width). Geographic distributions exclusive of drainages north of Ecuador and strong molecular phylogenetic evidence for a sister relationship between Andeancistrus and Transancistrus support the hypothesis that these genera may have once been contiguously distributed through a low-lying region of northern Peru and been separated via uplift of the Andes Mountains.