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Malaria is a leading and severe disease in Ethiopia, particularly like the Tigray region. The main objectives of the study were to model the influence of climate change on malaria transmission in Tigray and identify environmental variables that contribute to malaria. Aiming these objectives, Kafta Humera, Raya Azebo and Laelay Adiabo districts were purposively selected based on their malaria prevalence. Two hundred and nine mosquito occurrence points were collected from the study area. Collected occurrence points, altitude and 19 bioclimatic variables were run in Maxent software. Malaria transmission was simulated for themiddle and end of the twenty-first century using two representative concentration pathways (RCP4.5 and RCP8.5) scenarios driving ensemble of three general circulation models. The results show that the area suitable for malaria transmission is simulated to increase by 93.8% (RCP4.5) and 113.9% (RCP8.5) by mid-century and by 161% (RCP4.5) and 149% (RCP8.5) by the end of the twenty-first century, when compared with the historical baseline. This indicates that the area suitable for malaria transmission is simulated to increase due to climate change over the region. Therefore, the study recommends well prevention and control of malaria to ensure the health of people.