The present study evaluated the occurrence, antibiogram profile, and sequence types (STs) of multidrug resistant (MDR) Escherichia coli from freshly laid eggs (n = 480), feed (n = 24), water (n = 24), poultry droppings (n = 24), and hand swab samples (n = 10) collected from 24 deep litter (DL) and caged poultry layer farms (12 per category) across Punjab, India. The overall E. coli contamination rate in DL and cage farms was 32% (95% confidence intervals [CI], 26.6-37.8%) and 16.7% (95% CI, 12.6-21.6%), respectively. The logistic regression analysis revealed that the DL system had higher odds of occurrence (odds ratio [OR]) of extended-spectrum beta-lactamase (ESBL) (2.195, 95% CI, 1.065, 4.522) and ESBL/AmpC coproducers (2.69, 95% CI, 1.122, 6.45) compared to the cage system. Additionally, isolates from the DL were 4.065 (95% CI, 1.477, 11.188) times more tetracycline resistant compared to the latter; however, resistance to amoxyclavulanate (OR, 0.437; 95% CI, 0.209, 0.912), and ampicillin (OR, 0.343; 95% CI, 0.163, 0.720) was lesser in DL system. Notably, around 97.7% and 87.2% of the isolates from the DL and cage system were MDR, with the DL system having 6.439 (95% CI, 1.246, 33.283) times more chances of harboring MDR E. coli. Additionally, among the resistance genes, the DL system demonstrated significantly high presence of blaAmpC (56%), qnrA/B/S (42.3%), and tetA/B (30.6%). Furthermore, multilocus sequence typing of 11 MDR isolates (n = 5, DL, and 6, cage) revealed the presence of 10 STs, of which ST10, ST155, and ST156 were found to be of public health importance. Therefore, the present study highlights the burden of MDR, ESBL, and AmpC-producing E. coli on poultry eggs and farm environment, which could be carried over to human handlers and consumers upon direct contact during handling and processing.