This article predicts an unexpected positive effect of climate change on cotton production in Cameroon. Global warming could threaten cotton production in Africa due to increasing temperature and CO2, and rainfall uncertainties. This situation is worsened by the fact that most African farmers grow cotton as their cash crop and have few or no possible alternatives. Assessing the impact of climate change on cotton production is therefore critical. Here, we used CROPGRO, a process-based crop model that can simulate the main features of cotton growth and management. We applied this model to two regions in North Cameroon and a set of six regional climate projections combining general climate models and regional climate models from the ENSEMBLES project. The model was calibrated and validated with a data set of observations made in farmer fields from 2001 to 2005 and at an experimental station in 2010. Our results show unexpectedly that climate change from 2005 to 2050 in North Cameroon will have a positive effect on cotton yields with an increase of 1.3 kg ha?1 year?1 in yield, especially if conservation agriculture systems are adopted. The predicted increase of 0.05 °C year?1 in temperature will shorten crop cycles by 0.1 day year?1 with no negative effect on yields. Moreover, the fertilizing effect of CO2 enrichment will increase yields by approximately 30 kg ha?1. The rainfall pattern is likely to change, but the six regional models used to generate future weather patterns did not predict a decrease in rainfall. One model even forecast an increase in rainfall amounts. According to our findings, climate changes in North Cameroon can be anticipated by tailoring alternative cropping systems and adaptation techniques to cope with climate change.