The origin and early evolution of South American rodents are ongoing subjects of debate. The caviomorphs of the Peruvian localities of Santa Rosa and Contamana are the oldest South American rodents so far known. The Santa Rosa rodents are abundant and diverse, but dating was based on biostratigraphy (?Eocene), whereas in various Contamana sites radiometric dates, vertebrate biochronology and palynostratigraphy suggest an age of 41.6–40.94 Ma (late middle Eocene). Previous faunal comparisons between the localities have identified few shared taxa. Here we studied new and previously described rodent fossils from Santa Rosa and analysed their biochronological and biogeographical implications. We recognize five new taxa and three genera for Santa Rosa, four of them previously known only from the Eocene Contamana region. Thus, the Santa Rosa and the late middle Eocene Contamana assemblages appear to be chronologically closer than previously thought. An ?Eocene age for Santa Rosa is substantiated by other mammals reported from Santa Rosa. With 11 named genera and 15 species, the Santa Rosa rodents represent the most species‐rich South American Palaeogene rodent assemblage known. The Eocene radiation in the Neotropics that gave rise to this diversity was not associated with an immediate geographical dispersion to higher latitudes, perhaps because different biogeographical barriers or factors of competition delayed their dispersal. Evidence suggests that replacement, rather than a persistence of conservative long‐lasting lineages, was the dominant process among Palaeogene tropical caviomorph rodents.