Malaria is a major public health problem in India. The malaria transmission is sensitive to climatic parameters. The regional population-related factors also influence malaria transmission. To take into account temperature and rainfall variability and associated population-related effects (in a changing climate) on the malaria transmission over India, a regional dynamical malaria model, namely VECTRI (vector-borne disease community model) is used. The daily temperature and rainfall data derived from the historical (years 1961–2005) and representative concentration pathway (years 2006–2050) runs of the Coupled Model Intercomparison Project Phase 5 models have been used for the analysis. The model results of the historical run are compared with the observational data. The spatio-temporal changes (region-specific as well as seasonal changes) in the malaria transmission as a result of climate change are quantified over the India. The parameters related to the breeding cycle of malaria as well as those which estimate the malaria cases are analyzed in the global warming scenario.