The tropical rain forests of northwest South America fall within the Chocó-Darien Global Ecoregion (CGE). The CGE is one of 25 global biodiversity hotspots prioritized for conservation due to its high biodiversity and endemism as well as threats due to deforestation. The analysis of land-use and land-cover (LULC) change within the CGE using remotely sensed imagery is challenging because this area is considered to be one of the rainiest places on the planet (hence high frequency of cloud cover). Furthermore, the availability of high-resolution remotely sensed data is low for developing countries before 2015. Using the Random Forest ensemble learning classification tree system, we developed annual LULC maps in the CGE from 2002 to 2015 using a time series of cloud-free MODIS vegetation index products. The MODIS imagery was processed through a Gaussian weighted filter to further correct for cloud pollution and matched to visual interpretations of land cover and land use from available high spatial resolution imagery (WorldView-2, Quick Bird, Ikonos and GeoEye-1). Validation of LULC maps resulted in a Kappa of 0.87 (Sd = 0.008). We detected a gradual replacement of forested areas with agriculture (mainly grassland planted to support livestock grazing), and secondary vegetation (agriculture reverting to forest) across the CGE. Forest loss was higher between 2010-2015 when compared to 2002-2010. LULC change trends, deforestation drivers, and reforestation transitions varied according to administrative organization (countries: Panamanian CGE, Colombian CGE, and Ecuadorian CGE).