We present a high‐quality genome assembly for the Asiatic toad (Bufo gargarizans) and explore the evolution of several large gene families in amphibians. With a large genome assembly size of 4.55 Gb, the chromosome‐scale assembly includes 747 scaffolds with an N50 of 539.8 Mb and 1.79% gaps. Long terminal repeats (LTRs) constitute a high proportion of the genome and their expansion is a key contributor to the inflated genome size in this species. This is very different from other small amphibian genomes, but similar to that of the enormous axolotl genome. The genome retains a large number of duplicated genes, with tandem (TD) and proximal duplications (PD) the predominant mode of duplication. A total of 122 gene families have undergone significant expansion and were mainly enriched in sensory perception of smell and bitter taste. The CYP2C subfamily, which plays an important role in metabolic detoxification, specifically expanded via TD and PD in the Asiatic toad and the cane toad (true toads). Most of Na+/K+‐ATPase genes experienced accelerated evolution along Bufonid lineages and two amino acid sites involving toad‐toxin resistance were found to experience positive selection. We also revealed a dynamic evolution of olfactory and vomeronasal receptor gene families which was likely driven by the water‐to‐land transition. The high‐quality genome of the Asiatic toad will provide a solid foundation to understand the genetic basis of its many biological processes.