Cephalosporins and polymyxins are employed in antimicrobial protocols to control and treat neonatal infections and post-weaning diarrhoea in swine operations. We conducted a longitudinal study to evaluate the colonization and transmission of antibiotic–resistant Escherichia coli in sows and their piglets in a farrow-to-finish operation, focusing on characterization of Extended Spectrum Beta-Lactamase (ESBL) and mcr genes, virulence traits and genetic relatedness. A total of 293 E. coli isolates were obtained from faecal samples collected in five time points. At birth bla_CTX-M-1group cluster was detected in E. coli isolates from 9 sows and 49 piglets (73.41%), while in the following four’ piglets sampling moments it was detected in 91.8%, 57.6%, 71.4% and 97.4%. The gene mcr-1 was detected in E. coli from one sow and from three piglets from different litters at birth and increased in the first weeks of piglet life (68.85%, 100%, 90% and 8.1%). A new mcr-4 allele, mcr-4.7, was identified in 3.28%, 28.57%, 7.5% of E. coli isolates. Most mcr-positive E. coli isolates (96,7%) carried bla_CTX-M-1Group genes and 93,33% carried both mcr-4 and mcr-1. CTX-M-1 and CTX-M-32 were the most predominant ESBLs. Plasmids belonged to IncI1, IncF and IncN groups. Most isolates belong to phylogenetic group B1; PAI IV₅₃₆ marker was detected in nine isolates. The strains were kept in the different stages of the piglets’ life. The use of ceftiofur and colistin may explain the high prevalence and co-selection of bla_CTX-M-1Group and mcr-1 and/or -4 genes, contributing to the maintenance of resistant and virulent isolates throughout the pig life cycle that may reach the food chain.