Andean farmers, without our modern understanding of botany and genetics, utilized naturally occurring variation from mutation and sexual reproduction to establish landraces which they propagated from tubers. The origins and spread of potato cultivation through the Andes and into Southern Chile are relevant to the genetic base of modern cultivars and the need for genes from extant landraces to provide increased food security in many countries. As archaeological evidence is sparse and historical records are limited, we need to consider the current distribution of cultivated potatoes and their wild relatives and also analyse their DNA. Three key conclusions emerge. (1) Potatoes were first cultivated and domesticated from a few wild species in the high Andes of southern Peru, where the summers are cool and wet and daylengths are 12–13 h. (2) Although the first cultigen was a diploid potato, Group Stenotomum, it was the cultivation of tetraploid Group Andigena that spread throughout the Andes, and the genetically distinct tetraploid Group Tuberosum that became established in the longer days of Southern Chile. (3) There were natural hybridizations between cultivated potatoes and their wild relatives which could not subsequently occur elsewhere in the world in the absence of wild relatives.