Objectives: The public health threat of extended-spectrum \beta-lactamase (ESBL)-producing Escherichia coli continues to escalate, driven by rising resistance to common antibiotics and a dwindling pool of effective treatments. This laboratory-based cross-sectional study was designed to evaluate the phenotypic prevalence and antimicrobial resistance profiles of these clinical isolates using the automated VITEK 2 system. Methods: Over a two-month period (from February 18 to April 15, 2026), we collected and analyzed 75 unique clinical isolates of E. coli using the VITEK 2 platform integrated with the Advanced Expert System (AES). All statistical computations, including Pearson's chi-square and Fisher's exact tests, were carried out using IBM SPSS Statistics (v32), with significance set at P < 0.05.  Results: Of the 75 isolates evaluated, a striking 89.3% (67 isolates) were confirmed as ESBL producers. The vast majority of these samples originated from urine specimens (86.7%, 65/75). We observed that ESBL-positive strains carried significantly higher resistance rates to several key antibiotics, including piperacillin/tazobactam (P = 0.022), cefotaxime (P < 0.001), ceftazidime (P < 0.001), cefepime (P = 0.007), and ciprofloxacin (P = 0.003). Additionally, multidrug resistance (MDR) was highly prevalent, affecting 66.7% (50/75) of the isolates. On a positive note, imipenem, meropenem, and amikacin maintained excellent in vitro efficacy against almost all tested strains.  Conclusion: Our findings highlight a worrying prevalence of both phenotypic ESBL production and multidrug resistance among local clinical isolates of E. coli. While carbapenems and amikacin remain highly reliable therapeutic options, these results must be interpreted cautiously. The study's scope was bounded by certain limitations, such as a relatively small sample size, a heavy reliance on urine samples, geographical restriction to a single region, and the lack of molecular assays to identify specific ESBL resistance genes.