The increasing occurrence of virulent multidrug-resistant (MDR) avian pathogenic Escherichia coli (APEC) is of great concern to poultry industry. The present study was designed to monitor the occurrence and antimicrobial resistance patterns of MDR E. coli isolates and to gain insights into their virulence gene profile and the associated resistance genes. Forty-nine E. coli isolates (20%) were recovered from 242 samples collected from different sources in Egypt. Serotyping of all E. coli isolates revealed eight different serotypes with O114:K90 and O26:K60 being dominant (20% each). Multiple antibiotic-resistant phenotypes (>= 7 antibiotics) were alarmingly observed in all E. coli isolates, with the majority of isolates displaying resistance to amoxicillin-clavulanic acid, sulfamethoxazole-trimethoprim and erythromycin (100% each). Twenty-three different antibiotic resistance patterns were recognized in E. coli isolates with a predominant pattern of resistance to all antibiotics. We further found that resistant E. coli isolates to amoxicillin-clavulanic acid, ciprofloxacin, sulfamethoxazole-trimethoprim and streptomycin possessed bla(TEM), qnrS, sulI and aadA resistance genes (100%), respectively. Totally, blaTEM and sulI genes had the highest prevalence rates (100%). Evidentially, four or more virulence genes were noticed in 91% of E. coli isolates (multivirulent isolates), with iss (increase serum survival) being the most prevalent gene amplified on plasmid DNA of E. coli isolates (100%). Consequently, the association of antimicrobial resistance and virulence traits in MDR E. coli strains highlights the risk of promoting the spread of virulence through the extensive use of antibiotics in Egypt.