As multi-use conservation landscapes, biosphere reserves (BRs) exemplify the landscape mosaic approach to environmental decision-making. In this study, time-series remotely-sensed data (1993–2006–2012) were used to monitor vegetation transformation in the Kruger to Canyons Biosphere Reserve (K2C) of South Africa, updating previous land-cover research. We identified changes in spatial extent, rate and intensity of land-cover change and extrapolated observed trends to 2018. The increased rate of change in the recent observation period (2.3 vs. 5.7%) was driven by more intensive gains in impacted vegetation and settlement since 2006 (>210 km2 and >120 km2), with resultant transformation of intact habitat undermining regional connectivity. By 2012, intact vegetation had suffered losses of 6.3% (>350 km2) since 2006 and >14% (>750 km2) since 1993. A further 9.5% loss of intact habitat may represent a critical threshold, establishing K2C above the 50% threshold of landscape transformation, whereafter a rapid decline in landscape resilience is likely. Given the BR's spatial zonation, such a loss across the full extent of K2C is unlikely, at least in the short-term (i.e., by 2018). Yet, based on past trends of transformation in the unprotected transition zone, anticipating such losses in the longer term, is not unfounded (i.e., 2024).