Pharmaceuticals and personal care products (PPCPs) are known as an emerging class of water contaminants due to their potential adverse effects on aquatic ecosystems. In this study, we conducted the first nationwide survey to understand the distribution and environmental risk of 72 PPCPs in surface waterways of Sri Lanka. Forty-one out of 72 targeted compounds were detected with total concentrations ranging between 5.49 and 993 ng/L in surface waterways in Sri Lanka. The highest level of PPCP contamination was detected in an ornamental fish farm. Sulfamethoxazole was found with the highest concentration (934 ng/L) followed by N,N-diethyl-meta-toluamide (202 ng/L) and clarithromycin (119 ng/L). Diclofenac, mefenamic acid, ibuprofen, trimethoprim, and erythromycin were detected ubiquitously throughout the country. Our data revealed that hospital and domestic wastewater, and aquaculture activities potentially contribute to the presence of PPCPs in Sri Lankan waterways. The calculated risk quotients indicated that several locations face medium to high ecological risk to aquatic organisms from ibuprofen, sulfamethoxazole, diclofenac, mefenamic acid, tramadol, clarithromycin, ciprofloxacin, triclocarban, and triclosan. The aforementioned compounds could affect aquatic organisms from different trophic levels like algae, crustacean and fish, and also influence the emergence of antibiotic resistant bacteria. These findings emphasize that a wide variety of pharmaceuticals have become pervasive environmental contaminants in the country. This data will serve to expand the inventory of global PPCP pollution. Further monitoring of PPCPs is needed in Sri Lanka in order to identify PPCP point sources and to implement strategies for contaminant reduction in wastewater to protect the aquatic ecosystem, wildlife, and human health.