A new species of the Neotropical frog genus Odontophrynus from coastal regions of Brazil and Uruguay is described. It is included in the americanus species group and has a diploid complement of 22 chromosomes. Odontophrynus sp. nov. is distinguished from the other species of the americanus group by having smaller size, head nearly as wide as long, skin on dorsum bearing small-sized warts, and distinct postorbital and parotoid glands that form a longitudinal ridge. Moreover, the new species has a pair of enlarged postorbital dark blotches around the afore-mentioned glandular ridge and few small-sized dark blotches on the upper lip and forelimbs. Odontophrynus sp. nov. is also characterized by nasals and frontoparietals well separated from one another, frontoparietal fontanelle exposed anteriorly, and the maxillar process of nasals slightly separated from the nasal process of the pterygoids.