The ubiquity of pharmaceuticals and personal care products (PPCPs) and pesticides in aquatic environments has raised significant ecological concerns due to their potential to disrupt aquatic ecosystems. This study presents a high-throughput ultraperformance liquid chromatography-tandem mass spectrometry method without sample enrichment to monitor 323 PPCPs and pesticides in the surface water of the Jingmi Water Diversion Canal in Beijing, China. One hundred and three PPCPs and pesticides were detected, with the highest detection frequency observed for antibiotics, which constituted 25.2% of the total detections. Notably, the average concentrations of detected PPCPs and pesticides were significantly higher in the winter (69.0 ng/L) than in the summer (42.1 ng/L). Spatial characterization indicated higher concentrations of PPCPs and pesticides in urban areas compared with suburban areas, with carbendazim, caffeine, atrazine, and diazepam being the most frequently detected compounds. The ecological risk assessment based on risk quotient values identified moderate to high risks for aquatic organisms, particularly in urban areas and during winter. These findings highlight the necessity for improved wastewater treatment technologies and continuous environmental monitoring to protect aquatic ecosystems from the adverse effects of PPCPs and pesticides.