<p>A key target in the Kunming–Montreal Global Biodiversity Framework is to conserve at least 30% of global lands through protected areas and other effective area-based conservation measures to mitigate biodiversity loss. However, recent research indicates extensive habitat destruction within the global terrestrial protected area network and it is unknown how future, predictable risks of habitat destruction may severely undermine this target. Here, using high-resolution satellite datasets and machine learning models, we provide a global assessment of likely future human land-use expansion and associated natural habitat conversion risk within the terrestrial protected area estate under various socio-economic and climate scenarios. Human land use within protected areas is projected to rise by 27.50–51.17% by 2050 under four shared socio-economic pathway (SSP) scenarios. Consequently, 31.03–39.07% of terrestrial vertebrate species are expected to experience increases in human-dominated land uses inside protected areas. Protected areas in sub-Saharan Africa, South America and Southeast Asia are particularly at risk, where the need to balance food security, urbanization and biodiversity conservation presents substantial challenges. The SSP5-Representative Concentration Pathway 8.5 (RCP8.5) scenario is projected to exacerbate natural habitat conversion most severely, while SSP3-RCP7.0 and SSP2-RCP4.5 have comparatively lower impacts. Our findings underscore the necessity of addressing accelerated natural habitat conversion, ensuring the resilience of both existing and newly established protected areas against future threats.</p>