The increasing prevalence of antibiotic-resistant bacteria is an emerging problem for humans. Clinical misuse, overuse in agricultural and food settings, and limited numbers of new antibiotics have accelerated the proliferation of antimicrobial drug-resistant bacteria. To confront this threat, scientists must develop new therapeutics that eradicate these drug-resistant bacteria. In this study, we used Escherichia coli as an indicator organism to investigate antimicrobial drug and bacteriophage susceptibility. E. coli is a common, mostly benign, enteric, Gram-negative bacterial species that is commonly used to assess fecal contamination and water quality from environmental sources. We successfully isolated and cultured several E. coli strains from the Hans Groot Kill, a stream that runs through Union College’s campus, and known to be heavily contaminated with fecal coliform bacteria. We sought to assess whether these environmental isolates displayed antimicrobial drug and/or bacteriophage resistance and compared their patterns of susceptibility to known lab strains of E. coli. Using the lytic bacteriophage strains T4 and T4r, we conducted modified plaque assays with three E. coli environmental isolates and two lab strains “B” and “C.” The environmental isolates were found to be completely resistant to T4 and T4r, while their lab strain counterparts were susceptible. We also conducted Kirby-Bauer antimicrobial drug susceptibility tests with log phase-grown bacteria, using six Gram-negative targeted antimicrobial drugs (chloramphenicol, kanamycin, tetracycline, sulfamethoxazole, nalidixic acid, and nitrofurantoin). The lab strains were observed to be highly susceptible to all six antimicrobial drugs, while the environmental isolates showed partial resistance to some of them. These observed patterns of phage and antimicrobial drug resistance suggest that environmental E. coli strains must possess resistance mechanisms that could be exploited as a novel means of treating drug-resistant infections.