Avian pathogenic Escherichia coli (APEC) causes severe diseases in broiler chicken farms. This bacterial pathogen is associated with high mortalities in chickens and is considered the leading cause of human zoonotic disease. The present study aimed to investigate the prevalence and antimicrobial resistance profile of APEC in broiler chicken farms in Gharbia and Menofeya Provinces in Egypt. The study also evaluates the virulence associated factors and the genetic mechanisms of β-lactam antibiotics that are commonly used in the poultry industry in Egypt. In this study, 100 samples were collected randomly from 25 broiler chicken farms. Clinical symptoms and mortality rates were reported in the two districts of the central region of the Egyptian Delta. In total, 100 samples were collected from 25 broiler farms, and the overall prevalence of APEC infection reported in the study region was 30%. Isolated strains were serotyped as EHEC (8 O111: H4, 8 O128: H2 and 5 O127: H6) and ETEC (4 O44: H18 and 5 O125: H21). . The results revealed that APEC infection was significantly high in chickens older than four weeks old compared to younger than four weeks old. All tested isolates were sensitive to colistin and amikacin while all tested isolates were resistant to amoxicillin/clavulanic acid, ampicillin and sulfamethoxazole-trimethoprim. All tested isolates were resistant to spectinomycin except six strains of serotypes EHEC O111: H4 and O128: H2. On the contrary, all tested isolates were sensitive to cefotaxime except for six strains of EHEC O111: H4 and O128: H2. Furthermore, gentamycin was sensitive to all tested isolates except for EHEC O111: H4, O128: H2, and ETEC O44: H12. The phenotypically resistant E. coli against ampicillin, amoxicillin and cephalosporins harboured bla_TEM, bla_SHV, and bla_CMY2 as well as the following virulence genes, iss, eaeA, stx1 and stx2 were amplified in 12 (85.71%), 8 (57.14%), 2 (14.29%) and 1 (7.14%) isolate, respectively. Our findings suggest that farmers and veterinarians in the study area should use a standard treatment protocol for APEC to reduce the prevalence and antimicrobial resistance of this endemic disease. The efforts aimed at controlling and preventing such diseases will consequently lead to the minimal use of antibiotics on poultry farms.