Shigellosis is a major cause of morbidity and mortality among children, especially in developing countries. The increased extended-spectrum beta-lactamase (ESBL) resistance in Shigella poses a challenge for effective treatment. To examine the antibiotic resistance and ESBL profile of Shigella isolates from children with acute diarrhea. Shigella was isolated from stool cultures from pediatric patients suffering from acute diarrhea. The isolates were identified by bacteriological tests, serotyping, and multiplex polymerase chain reaction (PCR). The antimicrobial resistance was examined by disc diffusion. Phenotypic tests and PCR examined the ESBLs and CTX-M, SHV, and TEM genes. A total of 100 Shigella (10% prevalence rate) were isolated. The S. sonnei and S. dysenteries were the most prevalent species (33% and 31%, respectively), followed by S. flexneri (27%), and only 9% were S. boydii. The isolates had complete resistance (100%) to ampicillin. There was lower resistance to ciprofloxacin (24%), and no resistance to imipenem. By phenotypic tests, 54% of isolates had ESBL. By PCR, bla-CTX-M gene was the most prevalent (50%), followed by bla-TEM (48.1%). Only one isolate (1.9%) had the bla-SHV gene. The alarmingly high rates of antibiotic resistance and ESBL resistance among Shigella spp highlight the urgent need to restrict the unguided use of these drugs. Continuous monitoring of local and global antibiotic resistance patterns is required to prevent the spread of resistance.