Antibiotic residues and antimicrobial resistance in surface water are issues of global concern, especially in developing countries. In this study, the occurrence of seven antibiotics and one antiparasitic agent was determined in surface water samples collected from four rivers running through Hanoi urban area in the Red River Delta, northern Vietnam. The pharmaceuticals in water samples were analyzed by solid-phase extraction combined with liquid chromatography–tandem mass spectrometry method. The concentrations of pharmaceuticals in our samples ranged from 3050 to 16,700 (median 7800) ng/L, which were generally higher than levels found in river water from many other locations in the world. Amoxicillin, oxfendazole, and lincomycin were the most dominant and frequently detected compounds (detection rate 100%), which together accounted for 76 ± 14% of total concentrations. Sulfacetamide and sulfamethoxazole were detected at moderate concentrations in more than two-thirds of the analyzed samples. The remaining antibiotics (i.e., azithromycin, ciprofloxacin, and ofloxacin) were found at lower detection frequency and concentrations. Antibiotic concentrations in the water samples were not significantly different between the investigated rivers. Meanwhile, levels of pharmaceuticals in the samples collected in February 2020 were higher than those found in the remaining samples, largely due to the sharp decrease in sulfamethoxazole and azithromycin concentrations of the samples collected in March and April. Considerable ecological risks of antibiotics in surface water were estimated for some compounds such as amoxicillin, ciprofloxacin, and ofloxacin.