Abstract Effects of climate variability and change on yields of pearl millet have frequently been evaluated but yield responses to combined changes in crop management and climate are not well understood. The objectives of this study were to determine the combined effects of nutrient fertilization management and climatic variability on yield of pearl millet in the Republic of Niger. Considered fertilization treatments refer to (i) no fertilization and the use of (ii) crop residues, (iii) mineral fertilizer and (iv) a combination of both. A crop simulation model (DSSAT 4.5) was evaluated by using data from field experiments reported in the literature and applied to estimate pearl millet yields for two historical periods and under projected climate change. Combination of crop residues and mineral fertilizer resulted in higher pearl millet yields compared to sole application of crop residues or fertilizer. Pearl millet yields showed a strong response to mean temperature under all fertilization practices except the combined treatment in which yields showed higher correlation to precipitation. The crop model reproduced reported yields well including the detected sensitivity of crop yields to mean temperature, but underestimated the response of yields to precipitation for the treatments in which crop residues were applied. The crop model simulated yield declines due to projected climate change by −11 to −62% depending on the scenario and time period. Future crop yields in the combined crop residues + fertilizer treatment were still larger than crop yields in the control treatment with baseline climate, underlining the importance of crop management for climate change adaptation. We conclude that nutrient fertilization and other crop yield limiting factors need to be considered when analyzing and assessing the impact of climate variability and change on crop yields.