The environmental dissemination of selected antibiotics from hospital wastewater into municipal wastewater and lastly to a receiving water body was investigated. Selected antibiotics (azithromycin (AZM), ciprofloxacin (CIP), clindamycin (CDM), doxycycline (DXC) and sulfamethoxazole (SMZ)) present in effluents of academic hospital wastewater, influents, sewage sludge, and effluents of municipal wastewater, receiving water, and its benthic sediment samples were quantified using the Acquity® Waters Ultra-Performance Liquid Chromatography System hyphenated with a Waters Synapt G2 coupled to a quadrupole time-of-flight mass spectrometer. The overall results showed that all assessed antibiotics were found in all matrices. For solid matrices, river sediment samples had elevated concentrations with mean concentrations of 34,834, 35,623, 50,913, 55,263, and 41,781 ng/g for AZM, CIP, CDM, DXC, and SMZ, respectively, whereas for liquid samples, hospital wastewater and influent of wastewater had the highest concentrations. The lowest concentrations were observed in river water, with mean concentrations of 11, 97, 15, and 123 ng/L, except for CDM, which was 18 ng/L in the effluent of wastewater. The results showed that the highest percentages of antibiotics removed was SMZ with 90%, followed by DXC, AZM and CIP with a removal efficiency of 85%, 83%, and 83%, respectively. The antibiotic that showed the lowest removal percentage was CDM with 66%. However, the calculated environmental dissemination analysis through the use of mass load calculations revealed daily release of 15,486, 14,934, 1526, 922, and 680 mg/d for SMZ, CIP, AZM, DXC, and CDM, respectively, indicating a substantial release of selected antibiotics from wastewater to the river system, where they are possibly adsorbed in the river sediment. Further research into the efficient removal of antibiotics from wastewater and the identification of antibiotic sources in river sediment is needed.