Urban sprawl poses a significant threat to urban stream water quality due to impermeabilization, reduced vegetation cover, and the release of diffuse pollutants. This study evaluates water quality in seven catchments in Santo André, SP, considering seasonality. Nutrient concentrations and in situ measurements were taken during both dry and rainy seasons. Comparisons were made using Kruskal–Wallis and Mann–Whitney tests. Streams showed significant differences in relation to water quality parameters. The Carapetuba, Jundiaí, and Apiaí streams were most adversely affected, underscoring the need for urgent water quality intervention (water conductivity above 500 μS/cm, dissolved oxygen below 2 mg/L, total dissolved carbon above 50 mg/L, and total dissolved nitrogen above 25 mg/L). Significant differences were observed across seasons. The dry season showed elevated temperatures (above 25 °C) and increased total dissolved carbon (above 50 mg/L) and nitrogen concentrations (above 30 mg/L), indicating reduced dilution effects from rainfall and heightened organic contamination. Conversely, the wet season demonstrated lower nutrient concentrations, emphasizing seasonal dynamics. Sustained, long-term monitoring of urban streams in Santo André and the implementation of sewage collection and treatment in irregular settlements are recommended. These measures are essential to mitigate the adverse impacts of urban expansion on water quality.