The temperature response to anthropogenic global warming and forest cover changes is dependent on regional climatic characteristics. It is challenging to segregate the impacts of the two anthropogenic changes on local temperatures and heatwaves over complex mountainous regions. Here we present estimates of regional and local heat stress responses to the recent global climate change and local forest cover loss in complex terrain in the Himalayas using a satellite-based high-resolution land-surface temperature dataset. We find large-scale decreasing trends in the observed frequency of heatwaves and heat days, and localized increases in urbanized and high-elevation regions. Our results show large-scale significant decreasing trends in annual maximum and mean surface temperatures over the period 2003–2019. In locations that have witnessed large-scale forest losses, the declines in the surface temperatures were steeper compared to no-loss regions.We develop a regional multiple linear regression model to estimate the regional and local temperature responses to global climatic change and to segregate them from the response to forest cover losses. Our model estimates a regional decrease of about 2.0 °C in annual maximum temperature over the recent 2003–2019 period, which is locally modulated by the extent of urbanization, forest cover, and elevation. At the locations of intense deforestation, our model successfully predicts a steeper decrease in maximum surface temperature, and estimates the temperature response due to forest loss, after controlling for elevation and initial forest cover. The local cooling effect due to deforestation was reaffirmed by comparing the regions with contrasting forest cover losses. The results suggest that forest clearing amplifies the anthropogenic climate change over the region.