In the five chapters of this dissertation, I investigate the paleobiology of SouthAmerican native ungulates (SANUs) and caviomorph rodents. Although these studiesinvolve different taxonomic groups and employ disparate methods, most rely onpreviously undescribed fossils to interrogate broader evolutionary questions.In the first chapter, I describe early Miocene litopterns (a group of SANUs) fromPampa Castillo, Aysén Region, Chile, and perform a phylogenetic analysis of one of itssubgroups, Proterotheriidae. Litoptern taxa from Pampa Castillo include themacraucheniid Theosodon and proterotheriids Thoatherium and Picturotherium,corroborating the fauna’s assignment to the Santacrucian South American landmammal age (SALMA). My phylogenetic analysis, which indicates that“Anisolambdidae” forms a non-monophyletic cluster within Proterotheriidae, is thefoundation of a new stem-based definition for Proterotheriidae. This chapter waspublished in the Journal of Systematic Palaeontology in 2020.My second chapter describes two new proterotheriids from the middle Miocene ofQuebrada Honda, Tarija Department, Bolivia, and analyzes litoptern diversity and body size evolution in a phylogenetic context. These taxa, Olisanophus riorosarioensis gen.et sp. nov. and Olisanophus akilachuta gen. et sp. nov., greatly clarify proterotheriidevolution in mid-latitude South America. The diversity analysis indicates that thesegroups were more diverse than previously appreciated, particularly during thePaleogene. Macraucheniids increased in body size throughout the Cenozoic, whereasproterotheriids followed a similar trend during the Paleogene, but did not change in sizeduring the Neogene. This chapter was published in Ameghiniana in 2020.Cavioid, chinchilloid, and erethizontoid caviomorph rodents from Pampa Castilloare described in the third chapter. Cavioids are represented by Luantus minor, Eocardiacf. excavata, and Neoreomys australis, the last of which is the most abundantlyrepresented mammal in the Pampa Castillo fauna. Chinchilloids are represented by fourspecies of Perimys (P. erutus, P. onustus, P. intermedius, and a yet unnamed speciespreviously described from the Pinturas Formation), Prolagostomus pusillus, Scleromysquadrangulatus, and a probable new species of Scleromys. This assemblagerepresents a mixture of two well-known, contemporaneous fossil faunas previouslyrecognized from the lower + middle sequences of the Pinturas Formation and the SantaCruz Formation. The phylogenetic affinities and relative abundance of these taxasuggest the paleoenvironment of Pampa Castillo was similarly intermediate betweenthese two better-known faunas.In the fourth chapter, I describe the octodontoid caviomorphs from PampaCastillo and conduct a faunal similarity analysis of Pampa Castillo and ten other early tomiddle Miocene (Colhuehuapian–Friasian/Colloncuran SALMAs) Patagonian rodentfaunas. Eight octodontoids occur at Pampa Castillo, three of them likely representingnew species of Caviocricetus, Dudumus, and Prostichomys. The other five are referredto previously described taxa: Acarechimys minutus, Acarechimys constans,Acarechimys cf. minutissimus, Acaremys cf. murinus, and Spaniomys cf. riparius.Faunal similarity analyses yielded inconsistent results depending on whether genus- orspecies-level data were used. The combined results of these analyses and recentlypublished geochronological data suggest that the ‘Pinturan’ biochronologic interval isnot valid; faunas referred to it should instead be assigned to the Santacrucian SALMA.I analyze the proximal ankle bones of litoptern and notoungulate (another SANUgroup) from the early Miocene Santa Cruz Formation, Argentina with the aim ofassessing their utility in systematic studies and whether linear measurements or twodimensional(2D) landmarks are more effective for assessing morphological differences.The ultimate goal of this research is to allow robust inferences about the locomotoryhabits of the sampled taxa. These results suggest that isolated tarsals may be identifiedto family and genus-level, but this conclusion needs further testing. Quantitative testsshow that tarsals of different SANU taxa may be slightly more reliably distinguished by2D landmarks than by linear measurements. However, 2D landmarks are clearlysuperior from the perspective of ease of measurement, replicability, and applicability totaxonomically diverse samples. Although the lack of modern taxa in the sample limitedthe paleobiological inferences that could be drawn, body mass, phylogeny, and possiblylocomotor behavior, clearly influence tarsal morphology.Throughout this dissertation, I have used the description of new taxa andspecimens as the foundation for phylogenetic, paleoenvironmental, biochronological,and ecomorphological analyses. These studies have advanced our knowledge ofmammal evolution in South America, particularly in the early and middle Miocene.