Escherichia coli is one of the most common foodborne pathogens, increasingly contributing to antibiotic resistance, thereby posing a considerable challenge to the implementation of effective prevention management. Lactiplantibacillus plantarum is a probiotic with potent antibacterial and immune-boosting properties that can combat pathogenic E. coli through various mechanisms of action, offering an enormous potential for development. In this review, the research progress of L. plantarum against pathogenic E. coli is systematically reviewed. In addition, the mechanism of action of L. plantarum against E. coli both in vitro and in vivo is analyzed based on metabolizing active substances, mucosal barrier enhancement, competitive adhesion, and intestinal immune regulation. The applications of L. plantarum in animal husbandry, aquaculture, food processing, manufacturing, and clinical treatment are also summarized, providing insights into the use of probiotics in food safety and control.