Increasing sugarcane production to meet sugar industry demands is a major challenge facing agricultural sector in a more vulnerable environment to climate change in subtropical China. Numerous studies have shown the impact of climate change on sugarcane production, but most of these studies were conducted in a plot or catchment scale without assessing the impacts at regional scale. In this paper, climatic elements of temperature, rainfall, and radiation data, simulated by 28 global climate models, were evaluated using the Taylor chart. The two greenhouse gas emission scenarios, RCP4.5 and RCP8.5, were used to generate climate changes in the region. Combined with the spatial analysis method, the spatial and temporal variation of temperature, rainfall and radiation in Guangxi region from 2010 to 2100 were studied. A validated APSIM-sugarcane model was selected to simulate sugarcane yield at 22 research stations in Guangxi region under different RCP scenarios in the future, and to analyze the three research stages (2030s: 2021-2040; 2060s: 2051-2070 and 2090s: 2081-2100). The spatio-temporal changes of aboveground biomass weight (DM), sugarcane stalk and sucrose (S) yields of the years 2021-2100 were compared with those in the base years (1961-2010), and the effects of climate change on sugarcane yield were quantified. On average, the DM yields were projected to increase by 3.6 and 4.7 and 5.8 t ha−1 for RCP4.5 and 2.9, 5.4 and 8.5t ha−1 for RCP8.5 in 2030s, 2060s and 2090s as compared to 1961–2010, respectively. Similarly, the projected increase in S yields were 5.2, 7.0, and 8.3 t ha−1for RCP4.5 and 4.3, 7.2 and 10.8 t ha−1 for RCP8.5 in the respective future years in comparison with baseline years. The results showed that sugarcane yield had no significant relationship with changes in solar radiation, but the yield had significant correlations with rainfall and temperature changes. Combine changes in radiation, rainfall, temperature and elevated CO2 might be accounted for 69 and 76% changes in sugarcane DM and S yields, respectively, across the entire location. An increase in temperature caused a little increase in sugarcane yield, while an increase in rainfall increased sugarcane yields significantly, but decreased when it exceeded a certain limit. On the other hand, the S yield increased with increase in temperature at constant radiation, but decreased when the radiation exceeded a certain limit. Temperature changes only caused S yield increase when radiation and temperature increased simultaneously. The effects of temperature and rainfall on S yield were similar to those on biomass yield. The effects of radiation and rainfall on S yield showed that both rainfall and radiation increased S yields, but the amplitude was limited. Therefore, to mitigate climate change in the future, supplemental irrigation can be used to increase soil moisture content to improve sugarcane yield.