Climate is one of the major factors controlling agricultural productivity in Africa. Changes in meteorological variables such as rising temperatures, changes in precipitation and increase in atmospheric carbon dioxide levels affect crop production. The objective of this study was to evaluate the impacts of climate change and variability, and crop management on yield of maize (Zea mays L.) grown in the southern part of Tanzania. Using the Decision Support System for Agrotechnology Transfer Cropping System Model (DSSAT-CSM), a series of sensitivity experiments were conducted to evaluate the response of maize yields to a range of principal changes in rainfall and temperatures. The sensitivities were estimated under two management practices, one with traditional farming practices, and the other with application of external farm inputs. Dry-spells during the growing season caused yield losses of all cultivars of up to 43% for the prolonged dry-spells of 20 days. Increased rainfall intensity, during vegetative and reproductive stages, caused the decrease in yield of 5 and 2%, respectively. A 50-100% decrease in rainfall intensity during the growing season caused a loss of yields between 40-100%. Increased or decreased temperatures from the baseline values reduced or increased days to flowering and to physiological maturity, respectively. In addition, a decrease in temperature from the baseline values to 2 o C had an overall impact of yields loss for all cultivars. However, yields increased with an increase of temperature by up to 2.5 °C (UH6303 and H628) and 4.5 °C (PAN691). Growing seasons with lower total rainfall (<50 mm) and temperature (<1°C) from their climatological values, caused yield loss as much as 71 and 15%, respectively for PAN691 cultivar. Generally, the impacts depended on the management, cultivar, soil characteristics, magnitude, timing and duration of the stress.