The ‘arc of deforestation’ of southern Amazonia has one of the highest deforestation rates documented anywhere in the world. Landscape changes in a poorly studied but strategically important region in the Brazilian Amazon were studied using biennial Landsat TM/ETM+ images from 1984 to 2004. Deforestation rate for the period 1984–2004 was 2.47% yr−1 in the 7295 km2 study area, but decreased to 1.99% and 2.15% in 2000–2002 and 2002–2004, respectively. Landscape structure changes were characterized by smaller forest patches that were further apart, but increasingly complex in shape. Deforestation was mainly driven by cattle ranching, which in turn was affected by distance to roads, with forest cover increasing at greater distances from roads. A multi-layer perceptron was used to develop future scenarios based on Markov Chain analysis. Based on current land use, forest cover in the region will decline from 42% in 2004 to 21% by 2016. Results indicate a critical threshold at 51% of forest cover in which landscape structure and connectivity changes abruptly. This suggests that the region requires greater efforts in environmental law enforcement, land-use planning and education programmes to maintain the remaining forest cover near this threshold.