The accelerated spread of antimicrobial resistance, driven by the misuse of antibiotics in the context of ‘One Health’, is a public health concern worldwide due to the increasing number of human infections associated with foodborne and/or environmental pathogens, including multidrug-resistant Escherichia coli (E. coli). Monitoring pathogenic and multidrug-resistant E. coli isolates is essential for sustainable disease management in swine and human diarrhea cases. This study was designed to assess the multidrug resistance (MDR) profiles and virulence-associated gene (pathotypes) frequency of pathogenic and commensal E. coli strains by antimicrobial susceptibility testing and endpoint PCR among 983 E. coli isolates from swine fecal material and 425 stool isolates from human diarrhea cases, obtained from a closely monitored population between March 2015 and April 2016. Our results reveal that >50% of E. coli strains isolated from swine were resistant to nalidixic acid (78.94%), tetracycline (72%), ampicillin (55.54%), and co-trimoxazole (53.91%), and that, in humans, the highest resistance was observed in tetracycline (71.77%), nalidixic acid (65.41%), ampicillin (57.88%), and co-trimoxazole (53.88%). A lower frequency of resistance to ciprofloxacin was demonstrated in both swine (23.4%) and humans (15.3%), and minimal resistance to third-generation cephalosporins, ceftazidime (2.54%), and cefotaxime (2.44%) was observed in swine; however, resistance to these cephalosporins is much higher at 14.6% and 11.53% in humans. Among the pathotypes, EPEC was the most predominant (70.97%) in swine and DAEC (40%) in humans. In addition, pulsed-field gel electrophoresis separates the E. coli isolates into 22 patterns. Pathotypes such as EPEC and EHEC in swine highlight the need for surveillance and control in animal production to prevent zoonotic transmission. These results suggest that swine could act as a reservoir in human infection and that antimicrobial resistance could be transferred to humans from swine. Although we did not find clonal dissemination between the human and swine strains, the spread of similar multi-resistance profiles was observed, thus suggesting that multidrug resistance has been widely selected in this closed environment and may pose a public health risk.