The spread of antimicrobial-resistant pathogens is a global health concern. Most studies report high levels of antimicrobial resistance genes (ARGs) in the aquatic environment; however, levels associated with sediments are limited. This study aimed to investigate the distribution of ARGs in the sediments and water of the Akaki river in Addis Ababa, Ethiopia. The diversity and abundance of 84 ARGs and 116 clinically important bacteria were evaluated from the sediments and water collected from five sites in the Akaki river. Most of the ARGs were found in the city close to anthropogenic activities. Water samples collected in the middle catchment of the river contained 71-75% of targeted ARGs, with genes encoding aminoglycoside acetyltransferase (aac(6)-Ib-cr), aminoglycoside adenylyl transferase (aadA1), β-lactamase (blaOXA-10), quinolone resistance S (qnrS), macrolide efflux protein A (mefA), and tetracycline resistance (tetA), were detected at all sampling sites. Much fewer ARGs were detected in all sediments, and those near the hospitals had the highest diversity and level. Despite the lower levels and diversity, there were no unique ARGs detected in the sediments that were also not detected in the waters. A wide range of clinically relevant pathogens were also detected in the Akaki river. The findings suggest that the water phase, rather than the sediments in the Akaki river, is a potential conduit for the spread of ARGs and antibiotic-resistant bacteria.