Wild potato species have substantial phenotypic and physiological diversity. Here, we report a comprehensive assessment of wild and cultivated potato species based on genomic analyses of 201 accessions of Solanum section Petota. We sequenced the genomes of these 201 accessions and identified 6 487 006 high-quality single nucleotide polymorphisms (SNPs) from 167 accessions in clade 4 of Solanum section Petota, including 146 wild and 21 cultivated diploid potato accessions with a broad geographic distribution. Genome-wide genetic variation analysis showed that the diversity of wild potatoes is higher than that of cultivated potatoes, and much higher genetic diversity in the agronomically important disease resistance genes was observed in wild potatoes. Furthermore, by exploiting information about known quantitative trait loci (QTL), we identified 609 genes under selection, including those correlated with the loss of bitterness in tubers and those involved in tuberization, two major domesticated traits of potato. Phylogenetic analyses revealed a north-south division of all species in clade 4, not just those in the S. brevicaule complex, and further supported S. candolleanum as the progenitor of cultivated potato and the monophyletic origin of cultivated potato in southern Peru. In addition, we analyzed the genome of S. candolleanum and identified 529 genes lost in cultivated potato. Collectively, the molecular markers generated in this study provide a valuable resource for the identification of agronomically important genes useful for potato breeding. By utilizing genomic data of 201 accessions of Solanum section Petota, we investigated genetic variations of wild and cultivated potatoes and identified 609 selected genes presumably associated with artificial selection, domestication, or local adaption, including those involved in the loss of bitterness in tubers and those related to tuberization, two major domesticated traits of potato. The phylogenetic analysis supported the wild species S. candolleanum (endemic to southern Peru) to be the progenitor of cultivated potato. We further analyzed the S. candolleanum progenitor genome and identified 529 lost genes in cultivated potato during potato evolution.