This study examined the prevalence of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in river water samples (n = 56) and suspended solids (n = 5) from three major Western Cape rivers, in South Africa. Solid phase extraction (SPE) followed by liquid chromatography combined with electrospray tandem mass spectrometry (LC-MS/MS) using an analytical method developed in ISO 25101 (2009), PFOS and PFOA concentration in river water and in suspended solids from the rivers was investigated and quantified. From the results, PFOA and PFOS were detected in all the river water samples and were found in concentrations up to 314 and 182 ng/L for Diep River; 390 and 47 ng/L for Salt River; and 146 and 23 ng/L for Eerste River, respectively. In suspended solids, concentrations for PFOS and PFOA were 28 and 26 ng/g for Diep River; 16 and less than limit of detection for Eerste River; and 14 and 5 ng/g for Salt River, respectively. Some of these concentrations are higher than those previously reported in similar studies in various countries, and this suggests there is a cause for concern, in the Western Cape, South Africa, particularly in catchments where river and ground water is drawn for agricultural purposes in the province.