Abstract Forest reserves in Ghana are the only significant refugia of natural tropical forests, but they are threatened by land use pressures that have led to widespread forest degradation. Additional stress from climate perturbations, such as droughts, can reduce fuel moisture and lead to fires that render the reserves more vulnerable to further degradation. Here, we explore recent drought-associated wildfires in the forest zone of Ghana to better understand the combined effects of forest degradation and drought stress on fire in the forest reserves. We used remotely sensed Earth observations from MODIS and Landsat 8 along with Climate Hazards Group Infrared Precipitation with Stations (CHIRPS) precipitation data, to study fires that occurred during drought conditions in 2016. Fires were widespread in 2016, with an estimated 2137 km2 of forest reserve area burned. During the period 2003–2017, forest reserves experienced the most active fire detections in 2016. The majority of these fires were located in the moist semi-deciduous forests, the largest and most economically valuable forest type, accounting for more than 50% of all active fires and burned area. Forest reserves within the moist semi-deciduous forest type also had the highest standardized fire anomalies in 2016. There was a higher percentage of burned area in degraded forest reserves than in more intact reserves. These results underscore the vulnerability of Ghana’s forest reserves, particularly in the moist semi-deciduous type, to fires during severe droughts. Although drought predisposes moist tropical forests to fire, forest degradation also influences the spatial pattern and extent of burned forests. Fire-induced forest degradation presents a major challenge for conservation of humid tropical forests in the region. Within the context of REDD+ and other climate change mitigation and adaptation programs in West Africa, it will be imperative to incorporate effective fire management strategies into ongoing efforts to reduce forest degradation and sustain forest resilience.