Most anurans exhibit some degree of reduction in their dentition ranging from a lack of teeth in the lower jaws of frogs to complete edentulation in the true toads of the family Bufonidae. Tooth loss in vertebrates is unique in not only eliminating an anatomical structure, but also leading to the degeneration of a host of tooth-specific genes. Here we employ amelogenin (AMEL) pseudogenization as a tool to characterize the onset of tooth loss in toads. Comparison of AMEL from two members of the family Bufonidae: Rhinella marina and Bufo bufo with nine extant frog species revealed disruptive mutations indicative of AMEL inactivation in toads. dN/dS ratios, as a measure for selective pressure, confirmed neutral evolution in toad AMEL and purifying selection in frogs. Nonetheless, toad AMEL sequences were remarkably similar at 89.13%, with a moderate substitution rate, similar to comparably diverged frogs, while the ancestral branch leading to bufonids where tooth loss occurred exhibited a high number of mutations and tenfold higher substitution rate. Our calculations revealed that toad AMEL remained functional for only 1 – 5 million years after toads diverged from frogs ~80-100 million years ago. In conclusion, we found that AMEL pseudogenization involved temporary acceleration in substitution rate, rapid accumulation of inactivating mutations, and tooth loss shortly after the divergence of toads from frogs, indicative of early tooth loss in toads being an adaptive evolutionary process.