Protected areas (PAs) are a widely recognized tool for biodiversity and ecosystem conservation. However, megadiverse countries struggle to manage, maintain, and expand PAs as they face mounting human pressures. The Brazilian Cerrado biome (a biodiversity hotspot) is experiencing increasing land-use changes paired with a loss of natural vegetation, and only 3.2% of its land area is under strict protections. The Brazilian Long-Term Ecological Research Program (LTER) was created in 1997 to monitor long-term changes in protected and non-protected areas in Brazilian biomes. The Environmental Protected Area of the Gama and Cabeça de Veado (AGCV) watersheds in Central Brazil’s core distribution of the Cerrado (Brasília, Federal District), was one of the first sites to participate in the Brazilian LTER. The main goal of the AGCV-LTER site is to monitor long-term changes and ecological processes in aquatic and terrestrial ecosystems in PAs that are surrounded by landscapes facing extreme ecosystem shifts. Over 22 years, we investigated the effects of drivers such as fire, noise and light pollution, eutrophication, and biological invasions on aquatic (invertebrates and water quality) and terrestrial ecosystems (vegetation, vertebrates, and invertebrates). The results indicate that even within a PA, changes in the surrounding landscape affects biodiversity and ecosystem functions, revealing the essential nature of continuous monitoring for biodiversity conservation.