Sigmodontine rodents (Cricetidae, Sigmodontinae) represent the second largest muroid subfamily and the most species-rich group of New World mammals, encompassing above 410 living species and ca. 87 genera. Even with advances on the clarification of sigmodontine phylogenetic relationships that have been made recently, the phylogenetic relationships among the 12 main group of genera (i.e., tribes) remain poorly resolved, in particular among those forming the large clade Oryzomyalia. This pattern has been interpreted as consequence of a rapid radiation upon the group entrance into South America. Here, we attempted to resolve phylogenetic relationships within Sigmodontinae using target capture and high-throughput sequencing of ultraconserved elements (UCEs). We enriched and sequenced UCEs for 56 individuals and collected data from four already available genomes. Analyses of distinct data sets, based on the capture of 4,634 loci, resulted in a highly resolved phylogeny consistent across different methods. Coalescent species-tree based approaches, concatenated matrices, and Bayesian analyses recovered similar topologies that were congruent at the resolution of difficult nodes. We recovered good support for the intertribal relationships within Oryzomyalia; for instance, the tribe Oryzomyini appears as the sister taxa of the remaining oryzomyalid tribes. The estimates of divergence times agree with results of previous studies. We inferred the crown age of the sigmodontine rodents at the end of Middle Miocene, while the main lineages of Oryzomyalia appear to have radiated in a short interval during the Late Miocene. Thus, the collection of a genomic scale data set with a wide taxonomic sampling, provided resolution for the first time of the relationships among the main lineages of Sigmodontinae. We expect the phylogeny presented here will become the backbone for future systematic and evolutionary studies of the group.