Abstract Background Escherichia coli (E. coli) is a commensal flora of the gastrointestinal tract of humans and livestock animals. However, pathogenic and opportunistic variants are becoming a significant cause for concern in human healthcare (CDC, 2014). The emergence of these resistant strains is attributed to the overuse of antibiotics in agricultural practices (Llor, 2014). These microbes carry antimicrobial resistance (AMR) genetic markers that cause severe complications in treating intestinal and extra-intestinal infections in humans (Crecencio, 2020). The role of global meat industrialization and trade as a potential reservoir and source of transmission for AMR bacteria is considered a priority for OneHealth Initiatives, with collaborations between researchers, physicians, veterinarians, and food industries. Methods This study aims to compare the prevalence and antimicrobial susceptibility profiles of E. coli isolated from pork and poultry products imported from the USA to those domestically produced on the Caribbean Islands of St. Kitts and Grenada. This study was conducted over a 6-year period at the University of Medicine and Health Sciences (UMHS) in St Kitts and St. George’s University (SGU) in Grenada. Meat product samples were collected from retail stores around the Caribbean Islands. These meat samples were incubated at 36°C in Buffered media for 60 min and 24 h, then spread onto MacConkey agar to select for Gram-negative bacterial isolates. Lactose fermenting colonies were isolated and subcultured onto Nutrient agar. Species identification was performed using standard biochemical assays and Biomerieux API-20E test kits. Isolates were introduced to Mueller Hinton agar, and antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion. Results 100 meat product samples (50 domestic, 50 imported) were processed for investigation on the Caribbean Islands. On the Island of St. Kitts, 64 and 60 bacterial colonies were isolated from the domestic and imported samples, respectively. The prevalence of E. coli was 16% (n = 20) for imported samples and 12% (n = 15) for domestically produced samples. As Multiple drug resistance to >3 classes of antibiotics in E. coli isolates was 50% of imported isolates and 27% domestically produced. Resistance to amoxicillin was observed in 60% and 33% of E. coli isolates from Imported and Domestic origins, respectively. Resistance to trimethoprim-sulfamethoxazole was 25% and 13% in imported and domestic, respectively. Resistance to ciprofloxacin was 35% and 27% for imported and domestic, respectively. Resistance to cephalosporins was 60% in isolates from imported meat products and 33% in isolates from meat products domestically produced on the island of St. Kitts. Investigations are still ongoing for bacteria colony isolates from meat product samples from Grenada. Conclusion Imported meats products exhibit a higher prevalence of resistant E. coli, particularly in the beta-lactam class of antibiotics, including amoxicillin and cephalosporins. Therefore, the risk of importing meat products is a concern for introduction of AMR genetic markers to human populations. Active surveillance must be conducted to better understand the risk of exposure to humans from contaminated retail meat products to inform antibiotic therapy and resistance control continuously.