Introduction: Proteus spp. are opportunistic members of Enterobacteriaceae, accounting for 10% of urinary tract infections and other primary clinical infections. They produce extended-spectrum beta-lactamases (ESBL) that can confer resistance to beta-lactam antibiotics. This study aimed to investigate the prevalence, antimicrobial susceptibility, molecular characteristics, and genetic relationship of ESBL-producing Proteus spp. clinical isolates in Babol, Northern Iran. Methods: In this cross-sectional study, out of 112 clinical samples, 30 Proteus spp. isolates were identified via specific biochemical assays. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, antibiotic susceptibility was evaluated using disc diffusion and agar dilution methods, and polymerase chain reaction (PCR) was used to detect blaTEM and blaSHV genes. Results: The resistance rate to tetracycline and sulfamethoxazole was highest by disk diffusion and agar dilution. Multiple drug-resistant (MDR) isolates were 86% and 60% in disk diffusion and agar dilution assays. Seven (23.3%) isolates had the blaTEM genes and 18 (60%) blaSHV. Conclusion: ESBL-producing Proteus spp. was highly prevalent, and the blaSHV was the most common resistance contributing gene. These findings and relatively high resistance to ampicillin demand more care in prescribing antibiotics. Also, the high prevalence of MDR isolates in patients infected with ESBL-producing Proteus spp. requires continuous surveillance.