Background: The outcomes in critical illness depend on disease severity, practice protocols, workload, and access to care. This study investigates the factors affecting outcomes in mechanically ventilated coronavirus disease-2019 acute respiratory distress syndrome (COVID-19 ARDS) patients admitted in a tertiary teaching hospital intensive care unit (ICU) in Central India with reference to different time periods in pandemic. This is one of the largest series of mechanically ventilated COVID-19 ARDS patients, globally. Methods: This retrospective cohort study classified the entire data into four time periods (Period 1: April 2020 to June 2020; Period 2: July 2020 to September 2020; Period 3: October 2020 to December 2020; and Period 4: January 2021 to April 2021). We performed a multivariable-adjusted analysis to evaluate predictors of mortality, adjusted for baseline-severity, sequential organ failure assessment (SOFA score) and time period. We applied mixed-effect binomial logistic regression to model fixed-effect variables with incremental complexity. Results: Among the 56 survivors (19.4%) out of 288 mechanically ventilated patients, there was an up-gradient of survival proportion (0, 18.2, 17.4, and 28.6%) in four time periods. Symptom–intubation interval (OR 1.16; 95% CI 1.03–1.31) and driving pressures (DPs) (OR 1.17; 95% CI 1.07–1.28) were significant predictors of mortality in the model having minimal AIC and BIC values. Patients aged above 60 years also had a larger effect, but statistically insignificant effect favoring mortality (OR 1.99; 95% CI 0.92–4.27). The most complex but less parsimonious model (with higher AIC/BIC) indicated the protective odds of high steroid on mortality (OR 0.59; 95% CI 0.59–0.82). Conclusion: The outcomes in mechanically ventilated COVID-19 ARDS patients are heterogeneous across time windows and may be affected by the complex interaction of baseline risk and critical care parameters.