Changing climate conditions are supposed to have particularly strong impacts on agricultural production in the tropics with strong implications on food security. Ethiopia’s economy is profoundly dominated by agriculture, contributing to around 40% of the gross domestic product. Thereby, Ethiopia is one of the most vulnerable countries to the impact of climate change and has a wide gap in regional climate change impact studies. In this study, we systematically investigate climate change impacts on yields for the Gambella region in Ethiopia, exemplarily for maize. Here, we show how yields change until 2100 for RCPs 2.6, 4.5, and 8.5 from a climate model ensemble under rainfed and irrigated conditions. While rainfed yields decrease by 15% and 14% respectively for RCPs 2.6 and 4.5, yields decrease by up to 32% under RCP 8.5. Except for RCP 8.5, yields are not further decreasing after 2040–2069. We found that temperature increase, changing soil water availability, and atmospheric CO2 concentration have different effects on the simulated yield potential. Our results demonstrate the dominance of heat response under future climate conditions in the tropical Gambella region, contributing to 85% of total yield changes. Accordingly, irrigation will lose effectiveness for increasing yield when temperature becomes the limiting factor. CO2, on the other hand, contributes positively to yield changes by 8.9% for RCP 8.5. For all scenarios, the growing period is shorted due to increasing temperature by up to 29 days for RCP 8.5. Our results suggest that new varieties with higher growing degree days are primarily required to the region for adapting to future climate conditions.