Antimicrobial resistance (AMR) is one of the biggest threats to global health and food security worldwide. This study examined the prevalence, resistance patterns, and risk factors associated with Escherichia coli (E. coli) and Salmonella strains from poultry farms in Kelantan, Terengganu, and Pahang, Malaysia. A total of 371 samples (259=cloacal swabs, 84=faecal, 14=sewage and 14=tap water) were collected. Characteristics of the sampled farms including management type, biosecurity, and history of disease were first obtained using semi-structured questionnaire. In this regard, presumptive E. coli and Salmonella isolates were identified based on colony morphology with subsequent biochemical and Polymerase Chain Reaction confirmation (PCR). Susceptibility of isolates was also tested against a panel of 12 antimicrobials and interpreted alongside risk factor data obtained from the surveys. A total of 717 E. coli isolates were collected from the poultry and environmental samples. The findings showed that cloacal (17.8%, 46/259), faecal (22.6%, 19/84), sewage (14.3%, 2/14) and tap water (7.1%, 1/14) were significantly resistant to at least three antimicrobial classes (p < 0.003). In specific, resistance to tetracycline class was predominantly observed in faecal (69%, 58/84), cloacal (64.1%, 166/259), sewage (35.7%, 5/14), and tap water samples (7.1%, 1/84), respectively. Sewage water (Odds Ratio (OR) = 7.22, 95% Confidence Interval (CI) = 0.95–151.21) was observed to have a significant association with AMR acquisition. Multivariate regression analysis reveals that the risk factors including sewage samples (OR = 7.43, 95% CI = 0.96–156.87) and farm size are leading drivers of E. coli antimicrobial resistance in the participating states. Interestingly, we observed that the resistance patterns of E. coli isolates against 12 panel antimicrobials are generally similar in all the states. The highest prevalence of resistance was recorded in tetracycline (91.2%), oxytetracycline (89.1%), sulfamethoxazole/trimethoprim (73.1%), doxycycline (63%), and sulfamethoxazole (63%). In Salmonella samples, our findings revealed that isolates from faecal (15.5%, 13/84), cloacal (1.2%, 3/259), and sewage (7.1%, 1/14) samples were significantly resistant to at least five classes of antimicrobials. Resistance to Sulfonamides class (52%, 92/177) was predominantly observed followed by tetracycline (39.5%, 70/177), aminoglycosides (35.6%, 63/177), Penicillins (57/177, 32.2%) and Quinolones (45/177, 25.4%). Multivariate regression analysis identified intensive management system (OR = 1.55, 95% CI = 1–2.40) as a leading driver of AMR acquisition. The prevalence of resistance to common antimicrobials was recorded for sulfamethoxazole (33.9%), tetracycline (39.5%), and trimethoprim-sulphamethoxazole (37.9%). Different AMR genes were detected across all samples and their abundance in E. coli was higher in cloacal (20.8%, 10/48), faecal (16.7%, 8/48) and sewage (12.5%, 2/16) samples, and Salmonella spp. cloacal (35.4%, 17/48), faecal (23%, 11/48) and sewage (25%, 4/16) samples. A close association between different risk factors and the high prevalence of antimicrobial-resistant E. coli and Salmonella strains reflects an increased exposure to resistant bacteria thus raises a concern over rising misuse of veterinary antimicrobials that may contribute to the future threat of emergence of multidrug-resistant pathogen isolates. In summary, public health interventions to limit antimicrobial resistance need to be tailored to local poultry farm practices that affect bacterial transmission which include improvement of biosecurity and animal husbandry, increase the use of vaccines and strengthen surveillance systems, including developing alert mechanisms for early detection and reporting of AMR, public awareness and education, antimicrobial stewardship and medicinal regulation, as well as AMR research and fostering implementation research using One Health approach, is recommended.