Abstract The global significance of processed seafood necessitates vigilant monitoring for health risks, particularly in the ready-to-eat (RTE) sector. This study assessed the microbiological safety and antimicrobial resistance (AMR) profiles of 520 RTE seafood samples collected from Bayelsa, Nigeria. Escherichia coli identification was conducted using culture-based and polymerase chain reaction (PCR) methods. The isolates were further characterized using standard bacteriological techniques. PCR screening was employed to detect virulence and resistance genes. Of the processed RTE seafood samples assessed, 12.1% tested positive for E. coli. Extended-spectrum beta-lactamase (ESBL)-producing E. coli accounted for 2.3% of the samples. Various diarrheagenic determinants were identified, with aggregative adherence regulator-activated island (aaiC) and attaching and effacing (eae) being the most prevalent. Higher AMR levels were observed in ESBL-producing strains. Additionally, extracellular virulence factors, biofilm formation, and hydrophobicity assays revealed diverse pathogenic potentials among the isolates. The detection of beta-lactamase AMR genes, such as blaTEM (15.9%), blaCTX−M−15 (3.2%), and blaCTX−M−1 (1.6%), underscores the genetic mechanisms responsible for resistance in E. coli strains recovered from RTE seafood. These findings underscore the need for thorough monitoring and strict control procedures to ensure the safety of RTE seafood and mitigate the risks associated with AMR in food consumption.