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This study examines climate change, anthropogenic impacts, and their relationship with the sustainable development of the Brestnitsa karst geosystem. It is representative of the karst in Bulgaria, which is developed on a quarter of its territory. The geosystem approach was used to reveal the interrelationships in a typical karst territory. The data were collected from more than 10 years of integrated monitoring of the geosystem, including continuous instrumental monitoring in the show cave Saeva Dupka, which is part of the geosystem. Various data from other sources were also used, such as satellite observations (a digital terrain model, land cover, and satellite images and products), ground data, and climate reanalyses. A spatial analysis of the karst geosystem in the context of climate change and sustainable development was conducted using a complex of remote sensing methods, geographic information systems, and statistical methods. The main results include the state and trends in the climate of the area, changes and trends in the speleoclimate and gas composition of the air in the Saeva Dupka cave, and changes in land use in the territory of the geosystem. Conclusions about the connections between climate change, current karstogenesis, and the carbon cycle in the geosystem, as well as the response of the geosystem to the consequences of the combined impact of climate change and human activities, have been made. All these impacts on the karst geosystem have been assessed in order to make adequate management decisions to guarantee its sustainable development in the future. Full article