Cities in developing countries encounter rapid waves of social transformation and economic development where the environment is mostly a neglected aspect. The Katari watershed encompasses mining areas, El Alto city (one of the fastest growing urban areas in South America and the biggest in the Altiplano) as well as agricultural areas. Its outlet is Cohana Bay, one of the most polluted areas of Lake Titicaca. Here we propose an integrative approach (hydrological, physicochemical, chemical and bacterial data) to understand the pollution problem of this developing area, in which a variety of anthropogenic activities takes place. Both mining and urban areas appear to be sources of metal pollution. Nutrient and bacterial contaminations are mainly related to urban and industrial discharges. These situations have impacts in the basin from the mining area down to Cohana Bay of Lake Titicaca. Pollutant concentration patterns are highly influenced by seasonal hydrology variations. The poor quality of surface waters in the basin represents a risk for human and animal populations, as well as for the quality of aquifers located underneath El Alto city.