Introduction: Previous studies, including our research, provide critical insights into the contamination of food and water consumed by children under five in the Southern African Development Community (SADC) with Diarrheagenic Escherichia coli (DEC). Methods: This study uncovered the transmission dynamics of eleven DEC isolates from food, children under five and water from Maputo, Mozambique, with 125 others from the SADC region previously collected from food, animals and environment but available in the EnteroBase database ([http://enterobase.warwick.ac.uk](http://enterobase.warwick.ac.uk/)). The assemblies of the DEC isolates were analysed using pipelines at the Center for Genomic Epidemiology, Denmark. At the same time, statistical analysis and visualization were done using R-statistics. Results: Clustering based on Single Nucleotide Polymorphism (SNP) and core genome Multilocus sequence typing (cgMLST) alleles revealed associations based on geographic locations, sample niche, pathovar, and O:H antigen, pointing to evolutionary relatedness between the clades with Principal Coordinate Analysis uncovering this accounted for 27.55% of the genetic diversity. Virulence genes eae (63.97%), LT (25.00%), and Stx1 (15.44%) were most abundant, with an inverse association between the presence of LT and eae genes. Resistance to folate pathway antagonists (sulfamethoxazole– 55.9%), beta-lactamases (amoxicillin, ampicillin and piperacillin– all 54.4%), and aminoglycoside (streptomycin– 55.1%) were most abundant. Conclusions: The study provides insightful evidence on horizontal gene transfer and the risk associated with antibiotic and detergent resistance and virulent genes. We also provide a framework to facilitate a proactive response in the regional effort to protect human and animal health.