South-East Asian countries report a high prevalence of extended-spectrum cephalosporin- (ESC-) and colistin-resistant Escherichia coli (Col-R-Ec). However, there are still few studies describing the molecular mechanisms and transmission dynamics of ESC-R-Ec and, especially, Col-R-Ec. This study aimed to evaluate the prevalence and transmission dynamics of Ec containing extended spectrum beta-lactamases (ESBL) and mobile colistin resistance (mcr) genes using a 'One Health' design in Thailand. The ESC-R-Ec and Col-R-Ec isolates of human stool samples (69 pig farmers, 155 chicken farmers, and 61 non-farmers), rectal swabs from animals (269 pigs and 318 chickens), and the intestinal contents of 196 rodents were investigated. Resistance mechanisms and transmission dynamics of Ec isolates (n=638) were studied using short and long read sequencing. We found higher rates of ESBL-Ec isolates among pig farmers (n=36; 52.2%) than among chicken farmers (n=58; 37.4 %; P<0.05) and the control group (n=61; 31.1 %; P<0.05). Ec with co-occurring ESBL and mcr genes were found in 17 (6.0 %), 50 (18.6 %) and 15 (4.7 %) samples from humans, pigs and chickens, respectively. We also identified 39 (13.7 %) human samples with non-identical Ec containing ESBL and mcr. We found higher rates of ESBL-Ec, in particular CTX-M-55, isolates among pig farmers than among non-pig farmers (P<0.01). 'Clonal' animal-human transmission of ESBL-Ec and Ec with mcr genes was identified but rare as we overall found a heterogenous population structure of Ec. The Col-R-Ec from human and animal samples often carried mcr-1.1 on conjugative IncX4 plasmids. The latter has been identified in Ec of many different clonal backgrounds.