This study was conducted to determine the antibiotic resistance profile of Escherichia coli isolated from apparently healthy domestic livestock viz, cow, goats, and chicken from Akure, Ondo State Nigeria, E. coli was isolated using Eosin methylene Blue Agar (EMB) and identified by conventional microbiology technique. The isolate were tested against 14 antibiotics using the disc diffusion method. A total of 42 different antibiotics resistance profile were observed with each isolate showing resistance to at least four or more drugs tested. Generally the E. coli isolates showed resistance rates of 93.8% to ampicillin, 16.% to chloramphenicol, 57.5% to cloxacillin, 75.5% to Erythromycin, 20% to Gentamicin, 60.5% to penicillin, 19.5% to streptomycin, 25.8% to Ceftazidine, 45.8% to Cefuroxine,22.2% to cefixine 30.6% to Loxacin, 65.9% to augmentin, 26% nitrofurantoin, 29.3% to ciprofloxacin, 70.3% to tetracycline. This study showed that averages number of resistance phenotypes per isolate was significantly higher for goat and cow compared with poultry. A significant public health concern observed in this study is that multi drug resistance commena E. coli strains may constitute a potential reservoir of resistance genes that could be transferred to pathogenic bacteria