The Yolomécatl area, northwestern Oaxaca, Sierra Madre del Sur Morphotectonic Province, Mexico, lies between 17°25′N and 17°30′N latitude, 97°29′W and 97°36′W longitude, at 2200–2500 m above sea level, and includes ∼90km2 of rugged territory, where lithostratigraphic units of Late Jurassic to Quaternary age crop out. The Tertiary succession, which unconformably overlies Mesozoic formations, includes the Nduayaco ‘Group,’ a stack of intermediate lava flows, and the Yolomécatl Formation, a lacustrine/fluvial sequence ∼650 m thick, sparsely interbedded by tuff sheets. One tuff with an ⁴⁰Ar/³⁹Ar date of 40.3 ± 1.0Ma places this formation and the southernmost Eocene local fauna from North America in the late middle Eocene (Bartonian). The volcanic Nicananduta ‘Group’ (°27 Ma) overlies the Yolomécatl Formation. The Yolomécatl local fauna includes, among others, two new taxa: Douglassciurus oaxacaensis, sp. nov., so far the oldest sciurid in the world, and the enigmatic Protozetamys mixtecus, gen. et sp. nov., which despite its early age (late middle Eocene), already shows adaptations to process fibrous or abrasive food. If the caviomorph affinities of Protozetamys are correct, they would suggest dispersal northward of a South American rodent lineage. These finds strengthen the hypothesis that this region (southeastern Mexico) was a center of diversification and extend the record of Paleogene mammals southward °553 km (∼3°30′ latitude), i.e., from Marfíl, Guanajuato (in central Mexico), to Yolomécatl, Oaxaca (in southeastern Mexico).