Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 patients by using machine learning. Methods: This study included COVID-19 patients from Taipei Medical University-affiliated hospitals from May 2021 to May 2022. Sequential data on specific biochemical and ventilator parameters from days 0-2, 3-5, and 6-7 were analyzed to explore differences between the surviving (successfully weaned off the ventilator) and non-surviving groups. These data were further used to establish separate survival prediction models using random forest (RF). Results: The surviving group exhibited significantly lower mean C-reactive protein (CRP) levels and mean potential of hydrogen ions levels (pH) levels on days 0-2 compared to the non-surviving group (CRP: non-surviving group: 13.16 ± 5.15 ng/mL, surviving group: 10.23 ± 5.15 ng/mL; pH: non-surviving group: 7.32 ± 0.07, survival group: 7.37 ± 0.07). Regarding the survival prediction performanace, the RF model trained solely with data from days 0-2 outperformed models trained with data from days 3-5 and 6-7. Subsequently, CRP, the partial pressure of carbon dioxide in arterial blood (PaCO2), pH, and the arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio served as primary indicators in survival prediction in the day 0-2 model. Conclusions: The present developed models confirmed that early biochemical and ventilatory parameters-specifically, CRP levels, pH, PaCO2, and P/F ratio-were key predictors of survival for COVID-19 patients. Assessed during the initial two days, these indicators effectively predicted the likelihood of successful weaning of from ventilators, emphasizing their importance in early management and improved outcomes in COVID-19-related respiratory failure.