This article explores the impacts of climate change on the rural and natural landscapes at the Region of Eastern Macedonia and Thrace, Northeastern Greece. The spatial distributions of the bioclimatic de Martonne and phytoclimatic Emberger indices were calculated, at very high resolution (~500m), for the present conditions (1970–2000), two future time periods (2030–2060; 2070–2100) and for two greenhouse gas emission scenarios (RCP4.5; RCP8.5). The results show significant bioclimatic changes, especially in the Rhodope Mountain range and almost along the whole length of the Greek-Bulgarian border, where forests of high ecosystem value are located, together with the rural areas along the Evros river valley, as well as in the coastal zone of the Aegean Sea. The article describes the processes of bioclimatic changes that can significantly modify the landscapes of the study area. The study’s results reveal spatiotemporal shift towards more xerothermic environments under both scenarios. Independently of the employed indices, profound bioclimatic alterations are projected for the long-term timeframe of the extreme RCP8.5 scenario. According to the de Martonne outcomes, the more xerothermic Mediterranean and Semi-humid conditions are projected to impact the eastern, southern, and western agricultural landscapes (approximately 40% of the investigated area), the sustainability of which will depend on supplementary irrigation. Implementation of the Emberger index points out that by the year 2100, the natural and agricultural landscapes (distribution of ~ 42%) will be subjected to the Sub-humid, Mild winter, the Sub-humid, Cool winter (~33%) and the even more dry-thermal Humid/Sub-humid, Warm winter conditions (~5%). Based on these foreseen futures, initial interpretations for key landscape conservation, natural capital and ecosystem services management are proposed.