Intermittent rivers are becoming more ecologically stressed worldwide. Flow cessation occurs naturally and spatiotemporally in these systems and anthropogenic activities such as wastewater discharges can have considerable impacts. Public entities mostly monitor water quality in permanent streams, leading to insufficient monitoring of intermittent streams and consequently to their potentially inadequate management.. This study analyzed spatiotemporal patterns of water quality and associated ecological risk through the quantification of physicochemical and microbiological pollutants in the intermittent river system of El Novillo and San Marcos in Northeast Mexico. Results showed that water quality varied geographically and seasonally. Based on national and international criteria, annual averages of water quality parameters analyzed suggested that streamflow in these river systems is of poor quality and poses high ecological risk to aquatic life. In the urban area, annual mean concentrations of Cd and Pb (0.14 and 0.4 mg/L) were 77- and 10-fold higher than their respective water quality criteria (<0.0018 and 0.04 mg/L). Statistically significant (q < 0.05) correlations were identified in concentrations of cyanide, Cd, Cu and Pb between wastewater seeping into the river and streamflow within the urban area. These observations highlight the unique sensitivity of intermittent urban streams to anthropogenic activities and may provide useful information to enhance current water management plans for the El Novillo-San Marcos River system for the protection of ecosystem integrity and human health.