Campylobacter is one of the most important zoonotic bacterium and the leading cause of human gastroenteritis worldwide. To investigate the occurrence and antimicrobial resistance of this pathogen, a total of 360 chicken cloacal swabs and 15 water samples were gathered from different localities in Giza and Cairo Governorates. An additional 50 stool specimens were collected from individuals in contact with the examined chickens. Eleven Campylobacter isolates were recovered through bacteriological examination. Campylobacter spp. were identified by polymerase chain reaction (PCR) as C. jejuni (63.6 %) and C. coli (36.4 %) through the detection of the Map A and Ceu E genes, respectively. The antibiotic resistance of the Campylobacter isolates was determined via the disc diffusion method and was observed most frequently to nalidixic acid (81.8 %), tetracycline (72.7 %), ciprofloxacin (54.5 %), and erythromycin (54.5 %), while low resistance to ceftriaxone (18.2 %) was detected. Among the 11 Campylobacter isolates, 9 isolates were multidrug resistant (MDR). The tet (O) gene, which is responsible for tetracycline resistance, was detected in only 6 isolates. Phylogenetic analysis of the tet (O) gene sequences recovered from the C. jejuni isolates revealed that the strains isolated from chickens and drinking water from the same farm were identical. However, the sequence ofthe tet (O) gene from human isolates was highly similar to that from drinking water isolates. Our findings highlight the presence of MDR Campylobacter strains in chickens and the role of drinking water as a potential reservoir for tetracycline-resistant isolates. Therefore, regular monitoring of resistance is required, and increased attention should focus on preventing the transmission cycle of such emerging pathogens between different ecosystems to avoid public health hazards.