Antimicrobial resistance (AMR) is a growing global threat, undermining the efficacy of antibiotics and contributing to poor clinical outcomes. Escherichia coli (E. Coli), though typically a harmless gut commensal, plays a pivotal role in the carriage and spread of resistance genes through plasmid-mediated mechanisms. This review investigates three key AMR genes, QnrA, ErmB, and AAC(6’)-Ib-cr, in fecal E. Coli isolates. These genes confer resistance to fluoroquinolones, macrolides, and aminoglycosides, respectively, and are often embedded within mobile genetic elements, increasing their capacity for horizontal transfer across species and environments. Using molecular detection techniques, including conventional PCR, multiplex PCR, and qPCR, the study explores gene prevalence and public health implications in under-monitored regions, particularly Nigeria. Findings highlight the silent burden of AMR in asymptomatic carriers and emphasize the importance of fecal surveillance, integration of genomic tools, and One Health strategies. The study calls for routine gene-based monitoring and stricter regulation of antibiotic use to curb the spread of resistance determinants in both clinical and community settings.