Ceratophryidae is a family of frogs containing twelve extant species distributed in South America. Several studies have been carried out concerning the systematics, morphology, karyotypes, and behaviour within this monophyletic family. However, little is known about the historical biogeography and the divergence in time of this group. Here, we present an updated phylogeny, along with a calibrated chronogram, to analyse the historical biogeographical pattern and climate niche differentiation among extant species of Ceratophryidae (Anura: Hyloidea) frogs in South America. A phylogeny based on morphological and genetic data was obtained from 256 morphological characters, six mitochondrial and eight nuclear genes for up to a total of 8428 characters in the homological matrix. Our results indicate that the genus Ceratophrys is sister to the clade Chacophrys + Lepidobatrachus. The divergence of the crown group of Ceratophryidae is estimated to have occurred 19.2 Ma at the beginning of the Miocene, with recent cladogenetic events related to the late Miocene (10.18–13.70 Ma) and the Pliocene (~5.3–2.6 Ma). Moreover, the Cerrado region is estimated to be the ancestral area of the family, as well for the genera Chacophrys and Lepidobatrachus. In addition, temperature seasonality and annual precipitation play a major role in the niche differentiation of extant species within Ceratophryidae. In conclusion, our data suggest multiple dispersal and vicariance events originating from the Cerrado region in the early Miocene, and recognize the role of the environment in the differentiation of the ecological niches among extant species of this family in South America. Ceratophryidae is hypothesized to have originated in the semi-arid Cerrado region in the early Miocene (~19.2 million years ago), from where species have diversified by independent dispersal and vicariance events across other South American regions. Ceratophrys frogs are phylogenetically recovered as the sister taxon to the clade comprising Chacophrys and Lepidobatrachus. Three lineages of Lepidobatrachus and four lineages from Ceratophrys diverged in the Pliocene, around 5.3 to 2.6 million years ago. Niche differentiation among extant species of Ceratophryidae appears to reflect roles for temperature seasonality and annual precipitation.