COVID-19 scenarios were run using an epidemiological mathematical model (system dynamics model) and counterfactual analysis to simulate the impacts of different control and containment measures on cumulative infections and deaths in Bangladesh and Pakistan. The simulations were based on national-level data concerning vaccination level, hospital capacity, and other factors, from the World Health Organization, the World Bank, and the Our World in Data web portal. These data were added to cumulative infections and death data from government agencies covering the period from 18 March 2020 to 28 February 2022. Baseline curves for Pakistan and Bangladesh were obtained using piecewise fitting with a consideration of different events against the reported data and allowing for less than 5% random errors in cumulative infections and deaths. The results indicate that Bangladesh could have achieved more reductions in each key outcome measure by shifting its initial lockdown at least five days backward, while Pakistan would have needed to extend its lockdown to achieve comparable improvements. Bangladesh’s second lockdown appears to have been better timed than Pakistan’s. There were potential benefits from starting the third lockdown two weeks earlier for Bangladesh and from combining this with the fourth lockdown or canceling the fourth lockdown altogether. Adding a two-week lockdown at the beginning of the upward slope of the second wave could have led to a more than 40 percent reduction in cumulative infections and a 35 percent reduction in cumulative deaths for both countries. However, Bangladesh’s reductions were more sensitive to the duration of the lockdown. Pakistan’s response was more constrained by medical resources, while Bangladesh’s outcomes were more sensitive to both vaccination timing and capacities. More benefits were lost when combining multiple scenarios for Bangladesh compared to the same combinations in Pakistan. Clearly, cumulative infections and deaths could have been highly impacted by adjusting the control and containment measures in both national settings. However, COVID-19 outcomes were more sensitive to adjustment interventions for the Bangladesh context. Disaggregated analyses, using a wider range of factors, may reveal several sub-national dynamics. Nonetheless, the current research demonstrates the relevance of lockdown timing adjustments and discrete adjustments to several other control and containment measures.