BACKGROUND: The hystricognath rodents of the New World, the Caviomorpha, are a diverse lineage with a long evolutionary history, and their representation in South American fossil record begins with their occurrence in Eocene deposits from Peru. Debates regarding the origin and diversification of this group represent longstanding issues in mammalian evolution because early hystricognaths, as well as Platyrrhini primates, appeared when South American was an isolated landmass, which raised the possibility of a synchronous arrival of these mammalian groups. Thus, an immediate biogeographic problem is posed by the study of caviomorph origins. This problem has motivated the analysis of hystricognath evolution with molecular dating techniques that relied essentially on nuclear data. However, questions remain about the phylogeny and chronology of the major caviomorph lineages. To enhance the understanding of the evolution of the Hystricognathi in the New World, we sequenced new mitochondrial genomes of caviomorphs and performed a combined analysis with nuclear genes. RESULTS: Our analysis supports the existence of two major caviomorph lineages: the (Chinchilloidea + Octodontoidea) and the (Cavioidea + Erethizontoidea), which diverged in the late Eocene. The Caviomorpha/phiomorph divergence also occurred at approximately 43 Ma. We inferred that all family-level divergences of New World hystricognaths occurred in the early Miocene. CONCLUSION: The molecular estimates presented in this study, inferred from the combined analysis of mitochondrial genomes and nuclear data, are in complete agreement with the recently proposed paleontological scenario of Caviomorpha evolution. A comparison with recent studies on New World primate diversification indicate that although the hypothesis that both lineages arrived synchronously in the Neotropics cannot be discarded, the times elapsed since the most recent common ancestor of the extant representatives of both groups are different.