Objectives We conducted the present multicenter, retrospective study to assess the epidemiological, clinical, laboratory, and radiological characteristics associated with critical illness among patients with COVID-19 from Egypt. Methods The present study was a multicenter, retrospective study that retrieved the data of all Egyptian cases with confirmed COVID-19 admitted to hospitals affiliated to the General Organization for Teaching Hospitals and Institutes (GOTHI) through the period from March to July 2020. The diagnosis of COVID-19 was based on a positive reverse transcription-polymerase chain reaction (RT-PCR) laboratory test. Results This retrospective study included 2724 COVID-19 patients, of whom 423 (15.52%) were critically ill. Approximately 45.86% of the critical group aged above 60 years, compared to 39.59% in the non-critical group (p = 0.016). Multivariate analysis showed that many factors were predictors of critically illness, including age >60 years (OR = 1.30, 95% CI [1.05, 1.61], p = 0.014), low oxygen saturation (OR = 0.93, 95% CI [0.91, 0.95], p<0.001), low Glasgow coma scale (OR = 0.75, 95% CI [0.67, 0.84], p<0.001), diabetes (OR = 1.62, 95% CI [1.26, 2.08], p<0.001), cancer (OR = 2.47, 95% CI [1.41, 4.35], p = 0.002), and serum ferritin (OR = 1.004, 95% CI [1.0003, 1.008], p = 0.031). Conclusion In the present report, we demonstrated that many factors are associated with COVID-19 critical illness, including older age groups, fatigue, elevated temperature, increased pulse, lower oxygen saturation, the preexistence of diabetes, malignancies, cardiovascular disease, renal diseases, and pulmonary disease. Moreover, elevated serum levels of ALT, AST, and ferritin are associated with worse outcomes. Further studies are required to identify independent predictors of mortality for patients with COVID-19.