The earliest human settlements were those of llama and alpaca hunters, who left some remarkable rock paintings in Toquepala. The area attained its greatest development during the Tiahuanaco period. Known after 1625 as Villa de Santa Catalina de Guadalcazar del Valle de Moquegua, the regional capital became famous for its olives, pineapples, wines and brandies. Today mining is an important activity, and the port of Ilo is now the busiest in southern Peru .

The town has an attractive colonial-style centre and is surrounded by pleasant countryside.