The Salton Sea, the largest inland surface water body in California, has been designated as a sensitive ecological area by federal and state governments. Its two main tributaries, the New River and Alamo River are impacted by urban and agriculture land use wastes. The purpose of this study was to temporally and spatially evaluate the ecological risks of contaminants of concern in water, sediments and fish tissues. A total of 229 semivolatile organic compounds and 12 trace metals were examined. Among them Selenium, DDTs, PAHs, PCBs, chlorpyrifos and some current-use pesticides such as pyrethroids exceeded risk thresholds. From 2002 to 2012, measurements of chlorpyrifos in sediments generally declined and were not observed after 2009 at the river outlets. In contrast, pyrethroid concentrations in sediments rose consistently after 2009. In water samples, the outlets of the two rivers showed relatively higher levels of contamination than the main water body of the Salton Sea. However, sediments of the main water body of the Salton Sea showed relatively higher sediment concentrations of contaminants than the two rivers. This was particularly true for selenium which showed reductions in concentrations from 2002 to 2007, but then gradual increases to 2012. Consistent with water evaluations, contaminant concentrations in fish tissues tended to be higher at the New River boundary and at the drainage sites for the Alamo River compared to sites along each river. The persistent contaminants DDTs, PAHs, chlorpyrifos and several pyrethroid insecticides were associated with the toxicity of sediments and water collected from the rivers. Overall, assessment results suggested potential ecological risk in sediments of the Salton Sea as well as in water and fish from the two rivers.