Sao Tome and Principe is a small insular country in the west coast of Central Africa. The small dimensions of the islands and the limited natural resources put these islands under highly vulnerable to climate change. To assess the possible future impacts and risks on their agricultural activities, the high-resolution 4-km downscaled climate change projections using Eta regional climate model are used. A crop risk index (CRI) is proposed to assess the risk of climate change on cocoa (Theobroma cacao L.), pepper (Piper nigrum L. and Piper guinesse L.), taro (Colocasia esculenta (L.) Schott), and maize (Zea mays L.). The index takes into account the vulnerability to climate conditions and the crop yield in the future, and it is classified into very-high, high, moderate, low, and very-low. The climate change projections indicate increase in the risk of taro crop, partly due to thermal stress and partly due to the susceptibility to the leaf blight crop disease in taro. The risk of production of the pepper crop is very-high, mainly due to water stress. In mountain regions, the greater risk is due to the thermal stress caused by low temperatures. The cocoa crop is at risk due to water stress, mainly in the northwestern part of the Sao Tome Island, where major local production occurs. The projection indicates increase of the area with very-high risk to maize crops due to the increase of thermal stress and susceptibility to rust. In addition, in parts of the coastal regions, the risk changed from very-low to high risk, due to the low productivity potential. In general, the risks of the four major crops of Sao Tome and Principe increase in the future climate conditions.