Background: ISARIC mortality score is a risk stratification tool that helps predict the in-hospital mortality of COVID-19 patients. However, this tool was developed and validated in a British population, and thus, the external validation of this tool in local populations is important. Objectives: External validation of the ISARIC mortality score in COVID-19 patients from a large Saudi Arabian intensive care unit (ICU). Methods: This is a retrospective study that included all adult patients with COVID-19 admitted to the ICU of King Saud Medical City, Riyadh, Saudi Arabia, from March 2020 to June 2021. Patients who were pregnant or had pulmonary tuberculosis/human immunodeficiency virus were excluded along with patients with missing variables. Data were collected to calculate the ISARIC mortality score and then fitting receiver operator characteristic curve against patients’ outcome. Results: A total of 1493 critically ill COVID-19 patients were included. The mortality was 38%, the area under the curve of the score was 0.81 (95% confidence interval [CI]: 0.79–0.83, P < 0.001) and the cutoff value correctly classified 72.7% of the cohort. The cutoff value of >9 had sensitivity of 70.5% (95% CI: 66.6–74.3); specificity, 73.97% (95% CI: 71–76.8); positive predictive value, 62.4% (95% CI: 59.5–65.2) and negative predictive value, 80.2% (95% CI: 78.2–82.4). Conclusion: The ISARIC score was found to have excellent predictive ability for mortality in critically ill COVID-19 patients in our Saudi Arabian cohort. A cutoff score of >9 was the optimal criterion.