The Upper Guinea Forest (UGF) region of West Africa is one of the most climatically marginal and human-impacted tropical forest regions in the world. Research on the patterns and drivers of vegetation change is critical for developing strategies to sustain ecosystem services in the region and to understand how climate and land use change will affect other tropical forests around the globe. We compared six spectral indices calculated from the 20012015 MODIS optical-infrared reflectance data with manually-interpreted measurements of woody vegetation cover from high resolution imagery. The tasseled cap wetness (TCW) index was found to have the strongest association with woody vegetation cover, whereas greenness indices, such as the enhanced vegetation index (EVI), had relatively weak associations with woody cover. Trends in woody vegetation cover measured with the TCW index were analyzed using MannKendall statistics and were contrasted with trends in vegetation greenness measured with EVI. In the drier West Sudanian Savanna and Guinean Forest-Savanna Mosaic ecoregions, EVI trends were primarily positive, and TCW trends were primarily negative, suggesting that woody vegetation cover was decreasing, while herbaceous vegetation cover is increasing. In the wettest tropical forests in the Western Guinean Lowland Forest ecoregion, declining trends in both TCW and EVI were indicative of widespread forest degradation resulting from human activities. Across all ecoregions, declines in woody cover were less prevalent in protected areas where human activities were restricted. Multiple lines of evidence suggested that human land use and resource extraction, rather than climate trends or short-term climatic anomalies, were the predominant drivers of recent vegetation change in the UGF region of West Africa.