Water demand, pollution, and climate change threaten water security in industrialized and urbanized regions worldwide, especially in developing countries. Investments in massive infrastructure have often not met the water needs of the population, requiring water resource managers to adopt new approaches, such as decentralized and regionalized management at the micro-basin scale. However, little is known about the impact of anthropogenic activities on the water quality and vulnerability of streams that cross urban areas and feed into the main rivers and reservoirs supplying cities and industrial regions. The main goals of this research were to evaluate the water quality, pollutant loads, and effect of untreated sewage discharges in streams of the Piracicaba river basin, in the municipality of Americana, Southeast Brazil. The water quality parameters evaluated were as follows: pH, dissolved oxygen, electrical conductivity, biochemical oxygen demand, inorganic phosphorus, total phosphorus, total nitrogen, real colour, turbidity, total dissolved solids, metals (Ba, Cr, Cu, Ni, Pb, Cd, and Zn), total coliforms, and Escherichia coli. Descriptive statistics and multivariate analyses were performed. The results revealed chemical and biological degradation of the water resources, and vulnerability of the urban streams due to the release of untreated sewage into these waterways. The findings indicate the need for an immediate implementation of policies to monitor and control discharges of industrial effluents into the sewage collection systems, as well as discharges of sewage into rainwater drainage systems, together with the maintenance of green spaces.