This cross sectional study is aimed at evaluating the risk factors and antibiogram profiles of <i>Escherichia coli</i> O157:H7 in children stool and bovine meat obtained from selected households across Cross River State, Southern Nigeria. A total of 360 samples of fresh household bovine meat and 366 children diarrheal and nondiarrheal stool samples each were collected and examined for <i>E. coli</i> O157: H7 using standard culture and serological methods. Confirmed <i>E. coli</i> O157: H7 isolates were evaluated for antimicrobial susceptibility using the Agar disc diffusion method. The total positive samples for <i>E. coli</i> O157: H7 in household meat was 76/360 (21.11%,) while the diarrheaic and nondiarrheaic stool samples had 70/366 (19.13%) and 5/366 (1.37%) positive samples respectively. A significant difference was observed in the prevalence values among the bovine meat samples from various households and between the diarrheaic and nondiarrheaic samples at p<0.05. Risk factors such as <i>Age range</i> with highest prevalence value at 1-2yrs (26.83%); <i>Occupation of parent/guardian</i> with highest value from farming (25.67%) and <i>Main domestic water source</i> with highest value from surface water (28.21%) were observed to significantly affect the prevalence of the pathogen in children diarrheaic stool (p<0.05). All 70 diarrheaic isolates were resistant to one or multiple antibiotics with highest values obtained from tetracycline (88.6%) and cotrimoxazole (77.1%). This study revealed that bovine meat and some human and environmental factors play a vital role in the establishment of <i>E. coli</i> O157:H7 infection in children in the study communities with diarrheal stool being the main vehicle for secondary infections in humans. Cattle therefore serve as a major source of transmission of multi drug resistant <i>E. coli</i> O157:H7 to humans hence the need for continuous surveillance of this pathogen and implementation of legislation against indiscriminate use of antibiotics in diary farms.