Antimicrobial resistance (AMR) is an emerging public health problem worldwide. Agricultural practices have been suggested as one of the main contributors to the emergence and transmission of AMR worldwide. Aquatic animals like fish have an important role to play in the emergence and transmission of AMR strains. Escherichia coli is commensal in gastrointestinal tracts of many animals including fish, and is an indicator organism and opportunistic pathogen. It has been listed as one of the important bacteria involved in the emergence and spread of antimicrobial resistance factors. The objective of this study was to investigate the AMR patterns of E. coli isolated from the intestinal tract of fish within the Lake Victoria basin. A total of 60 Oreochromis niloticus fish were sampled from cages, wild and earthen ponds. Distal gastrointestinal tract was recovered, crushed and streaked on violet red bile agar, incubated at 37 O C for 24 hours. The isolates confirmed biochemically as E. coli were screened for antibiotic susceptibility against 10 commonly used antibiotics using disc diffusion method. Eighty three percent of the sampled fish were positive for E. coli. Generally, isolates were susceptible to ciprofloxacin, gentamicin, cephalexin, ceftriaxone and nitrofurantoin (100%); tetracycline, sulfamethoxazole-trimethoprim (81.8%) and nalidixic acid (72.7%). However, most of them were resistant to ampicillin and erythromycin (72.7%). The results show that fish are reservoirs of E. coli, which is resistant to some antibiotics. The factors responsible for the observed resistance patterns need to be followed up with more research. Good aquaculture practices, surveillance and monitoring of resistant bacteria will help in understanding the problem of AMR.