Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infections (UTIs) in hospitalised and non-hospitalised patients. Genomic analysis was used to gain further insight into the molecular characteristics of UPEC isolates from Saudi Arabia. A total of 165 isolates were collected from patients with UTIs between May 2019 and September 2020 from two tertiary hospitals in Riyadh, Saudi Arabia. Identification and antimicrobial susceptibility testing (AST) were performed using the VITEK system. Extended-spectrum β-lactamase (ESBL)-producing isolates (n = 48) were selected for whole genome sequencing (WGS) analysis. In silico analysis revealed that the most common sequence types detected were ST131 (39.6%), ST1193 (12.5%), ST73 (10.4%), and ST10 (8.3%). Our finding showed that bla_CTX-M-15 gene was detected in the majority of ESBL isolates (79.2%), followed by bla_CTX-M-27 (12.5%) and bla_CTX-M-8 (2.1%). ST131 carried bla_CTX-M-15 or bla_CTX-M-27, and all ST73 and ST1193 carried bla_CTX-M-15. The relatively high proportion of ST1193 in this study was notable as a newly emerged lineage in the region, which warrants further monitoring.