Aerosols emitted in densely populated and industrialized Indo-Gangetic Plain, one of the most polluted regions in the world, modulate regional climate, monsoon, and Himalayan glacier retreat. Thus, this region is important for understanding aerosol perturbations and their resulting impacts on atmospheric changes during COVID-19 lockdown period, a natural experimental condition created by the pandemic. By analyzing 5 years (2016–2020) data of aerosols and performing a radiative transfer calculation, we found that columnar and near-surface aerosol loadings decreased, leading to reductions in radiative cooling at the surface and top of the atmosphere and atmospheric warming during lockdown period. Further, satellite data analyses showed increases in cloud optical thickness and cloud-particle effective radius and decrease in lower tropospheric air temperature during lockdown period. These results indicate critical influences of COVID-19 lockdown on regional climate and water cycle over Indo-Gangetic Plain, emphasizing need for further studies from modeling perspectives.