<p>The frog genus <i>Odontophrynus</i> comprises 10 species arranged in three species groups that inhabit southeastern South America. In Argentina, it is represented by the <i>O. americanus</i> and <i>O. occidentalis</i> species groups and, despite being a fairly common taxon of the extant herpetofauna, it has no known fossil record. Here we report on the first fossil record of the genus, based on an almost complete right ilium from the lower levels of the Buenos Aires Formation (OIS 11, Bonaerian age, middle Pleistocene) in the Bonaerian Pampas of Argentina. The taxonomic allocation is derived from a thorough survey of anuran ilia and is grounded in a set of distinct ilial characters that, in combination, do not occur in any other anuran. These include: ilium not fused to ischium; well-developed dorsal acetabular expansion; broad preacetabular zone with a shallow preacetabular fossa; straight ilial shaft lacking dorsal ridge; and spike-like dorsal prominence bearing a distinct dorsal protuberance. Additionally, after comparing with a large sample of specimens representing most species of <i>Odontophrynus</i>, we propose two main characters (high spike-like dorsal prominence, absence of a lateral knob on the dorsal prominence) that allow referral to <i>Odontophrynus</i> aff. <i>O. americanus</i> or <i>O. cordobae</i>.</p> <p>SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at <a href="http://www.tandfonline.com/UJVP" target="_blank">www.tandfonline.com/UJVP</a></p> <p>Citation for this article: Turazzini, G. F., M. L. Taglioretti, and R. O. Gómez. 2016. First fossil record of the South American frog genus <i>Odontophrynus</i> Reinhardt and Lütken, <a href="#cit0031" target="_blank">1862</a> (Anura, Neobatrachia). Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2017.1228657.</p