Cereal crop production in sub-Saharan Africa has not achieved the much-needed increase in yields to foster economic development and food security. Maize yields in the region’s semi-arid agroecosystems are constrained by highly variable rainfall, which may be worsened by climate change. Thus, the Tanzanian government has prioritized agriculture as an adaptation sector in its intended nationally determined contribution, and crop management adjustments as a key investment area in its Agricultural Sector Development Programme. In this study, we investigated how future changes in maize yields under different climate scenarios can be countered by regional adjusted crop management and cultivar adaptation strategies. A crop model was used to simulate maize yields in the Singida region of Tanzania for the baseline period 1980–2012 and under three future climate projections for 2020–2060 and 2061–2099. Adaptation strategies to improve yields were full irrigation, deficit irrigation, mulch and nitrogen addition and another cultivar. According to our model results, increase in temperature is the main driver of future maize yield decline. Increased respiration and phenological development were associated with lower maize yields of 16% in 2020–2060 and 20% in 2061–2099 compared to the 1980–2012 baseline. Surprisingly, none of the management strategies significantly improved yields; however, a different maize variety that was tested as an alternative coping strategy performed better. This study suggests that investment in accessibility of improved varieties and investigation of maize traits that have the potential to perform well in a warmer future are better suited for sustaining maize production in the semi-arid region than adjustments in crop management.