Snake’s numerous fascinating features distinctive from other tetrapods necessitate a rich history of genome evolution that is still obscure. To address this, we report here the first high-quality genome of a viper, Deinagkistrodon acutus and comparative analyses to other species of major snake lineages and lizard. We mapped the evolution trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. Besides the dynamic lineage-specific expansion, many TEs may have been rewired into the regulatory network of brain genes in viper, indicated by the associated expression of TEs and nearby genes restricted to the brain. We characterized signatures of adaptive evolution in olfactory, venom and thermal-sensing genes, and also functional degeneration in genes associated with vision and hearing. Phylogenetic distribution of the degenerating Hox and Tbx limb-patterning genes support a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we showed snake Z and W sex chromosomes have undergone at least three times of recombination suppression at the ancestor of advanced snakes, with the W chromosomes forming a gradient of degeneration from basal snakes to advanced snakes. These results, together with all the genes identified as undergoing adaptive or degenerative evolution episodes at respective snake lineages forge a framework for our deep understandings into snakes’ molecular evolution history.