This study was to evaluate the level of contamination of surface waters by coliform bacteria and Escherichia coli, as well as to detect the fecal pollution and the antibiotic resistance patterns of E. coli strains from recovered Asi (Orentes) River in the southern region of Turkey. Total and fecal coliform results were revealed as ˃1100 MPN/100 mL and 1100 MPN/100 mL for two stations, respectively. A total of 10 E. coli isolates were screened for antibiotic susceptibility by Kirby Bauer method. Resistance to cefotaxime, tobramycin, streptomycin, trimethoprim, cefepime, cefazolin, and ampicillin was determined in 20%, 20%, 40%, 20%, 20%, 20%, and 40%, respectively. These findings point out a widespread distribution of E. coli strains produced antibiotic resistance genes in the surface waters in the southern region of Turkey, suggesting an aquatic reservoir for resistance genes. Multiple antibiotic resistance (MAR) rates of %30 of E. coli isolates were greater than 0.200. This high index indicates exceeding the permissible water quality limits for human use and consumption and is the primary source of contamination in the discharges from domestic, agricultural, and urban.