Among contaminants of emerging concern in the environment, a growing attention has been given to antibiotics and antibiotic-resistant genes (ARGs) due to the rise in their usage and potential ecotoxicological and public health effect. However, the occurrence of these contaminants in the environment is little investigated in developing countries particularly in sub-Saharan regions. In this study, the occurrence of three groups of antimicrobials including tetracycline, sulfonamides and fluoroquinolone, and their corresponding ARGs were investigated in the sediments of Awash River Basin, Ethiopia. Out of twelve studied compounds, sulfadiazine and enrofloxacin showed the highest and lowest detection frequency, respectively. Polymerase chain reaction (PCR) analysis revealed that tetA and tetB occurred in all the samples. The relative abundance of the resistant genes was in the following order: tetA > tetB > sul2 > sul1. Redundancy analysis result indicated that some sediment characteristics were found to have influence on the distribution sul1-resistant gene.