India enforced stringent lockdown measures on March 24, 2020 to mitigate the spread of the Severe Acute Respiratory Syndrome Coronovirus-2 (SARS-CoV-2). Here, we examined the impact of lockdown on the air quality index (AQI) [including ambient particulate matter (PM and PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), ozone (O), and ammonia (NH)] and tropospheric NO and O densities through Sentinel-5 satellite data approximately 1 d post-lockdown and one month pre-lockdown and post-lockdown. Our findings revealed a marked reduction in the ambient AQI (estimated mean reduction of 17.75% and 20.70%, respectively), tropospheric NO density, and land surface temperature (LST) during post-lockdown compared with the pre-lockdown period or corresponding months in 2019, except for a few sites with substantial coal mining and active power plants. We observed a modest increase in the O density post-lockdown, thereby indicating improved tropospheric air quality. As a favorable outcome of the COVID-19 lockdown, road accident-related mortalities declined by 72-folds. Cities with poor air quality correlate with higher COVID-19 cases and deaths (r = 0.504 and r = 0.590 for NO; r = 0.744 and r = 0.435 for AQI). Conversely, low mortality was reported in cities with better air quality. These results show a correlation between the COVID-19 vulnerable regions and AQI hotspots, thereby suggesting that air pollution may exacerbate clinical manifestations of the disease. However, a prolonged lockdown may nullify the beneficial environmental outcomes by adversely affecting socioeconomic and health aspects.