Extended data and supplementary information are available at https://doi.org/10.1038/s41588-019-0522-8Melonis an economically important fruit crop that has been cultivated for thousands of years; however, the genetic basis and history of itsdomesticationstill remain largely unknown. Here we report acomprehensive mapof the genomicvariationinmelonderived from the resequencing of 1,175 accessions, which represent the global diversity of the species. Our results suggest that three independentdomestication eventsoccurred inmelon, two in India and one in Africa. We detected two independent sets ofdomesticationsweeps, resulting in diverse characteristics of the two subspecies melo and agrestis duringmelonbreeding.Genome-wide association studies for 16agronomic traitsidentified 208locisignificantly associated with fruit mass, quality and morphological characters. This study sheds light on thedomesticationhistory ofmelonand provides a valuable resource for genomics-assisted breeding of this important crop.