Three new genera of Baetidae (Ephemeroptera) are described from larvae from South America. Adebrotus Lugo-Ortiz & McCafferty, n.gen., and its type species, A. amazonicus Lugo-Ortiz & McCafferty, n.sp., were taken from Amazonas, Brazil. The genus possesses numerous unique mouthpart characteristics, including a labrum with distinct anteromarginal protrusions, a left mandible with the inner incisors rotated to a right angle with the flat plane of the mandible, a right mandible with a large denticle in the midregion of the mola, unusually shaped galealaciniae with distally pectinate setae, and an unusually shaped labium. Tomedontus Lugo-Ortiz & McCafferty, n.gen., and its type species, T. primus Lugo-Ortiz & McCafferty, n.sp., were taken from Amazonas and Pará, Brazil. The genus possesses a trapezoidal labrum lacking an anteromedial emargination, a distomedial process on the hypopharyngeal superlinguae, laterally denticulate mandibles, and unusually shaped maxillae and labium. Waltzoyphius McCafferty & Lugo-Ortiz, n.gen., and its type species, W. fasciatus McCafferty & Lugo-Ortiz, n.sp., were taken from Amazonas and Pará, Brazil, and Paraguarí, Paraguay. The genus is distinct in that the maxillae have only falcate denticles on the galealaciniae, the labium is unusually shaped, and the midsternum has an acute medial spur.