The Escherichia coli that produces extended-spectrum lactamases (ESBL-E. coli) can develop resistance to many antibiotics. The control of ESBL-E. coli disorders is challenging due to their restricted therapeutic approaches, so this study aims to determine the prevalence and pattern of the antibiotic resistance of ESBL-E. coli among male and female patients with urinary tract infections in Riyadh, Saudi Arabia. During the period of 2019 to 2020 at King Fahd Medical City, Riyadh, 2250 urine samples from patients with urinary tract infections (UTIs) were collected, and microbial species were cultured and identified using standard biochemical techniques. A double-disc synergy test was used to identify ESBL-producing strains of E. coli, and an in vitro method and the clinical laboratory standard institute (CLSI) criteria were employed to determine the resistance of these strains to antimicrobial drugs. ESBL-E. coli was detected in 510 (33.49%) of the 1523 E. coli isolates, 67.27% of which were recovered from women and 33.7% of which were recovered from men. A total of 284 (55.69%) ESBL-E. coli isolates were found in patients under 50 years of age, and 226 (44.31%) were found in patients over 50 years of age. Nearly all the isolates of ESBL-E. coli were resistant to cephalosporins (ceftriaxone, cefotaxime, cefepime, cefuroxime, and cephalothin) and penicillin (ampicillin), whereas the majority of the isolates were sensitive to several carbapenems (imipenem, meropenem, and ertapenem), aminoglycosides (amikacin), and nitrofurantoins. The development of antibiotic resistance by ESBL-E. coli, the most frequent pathogen linked to urinary tract infections, plays a crucial role in determining which antibiotic therapy is appropriate.