High temperature and drought stress are among the two most important environmental factors influencing crop growth, development and yield processes. These two stresses commonly occur in combination. Objectives of this research were to investigate the independent and combined effects of high temperature and drought stress during grain filling on physiological, vegetative and yield traits and expression of a chloroplast protein synthesis elongation factor (EF-Tu) of wheat (Triticum aestivum L.). Two spring wheat cultivars (Pavon-76 and Seri-82) were grown at control temperatures (CT; day/night, 24/14 °C; 16/8 h photo/dark period) from sowing to heading. Thereafter, one half of the plants were exposed to high temperature stress (HT; 31/18 °C in Exp. 1 and 34/22 °C in Exp. 2), drought stress (withholding water), or a combination of both HT and drought stress. There were significant influences of HT and/or drought stress on physiological, growth and yield traits. There was no cultivar or cultivar by temperature or cultivar by drought interaction effects on most traits. The decreases in leaf photosynthesis were greater at HT compared with drought alone throughout the stress period, and the combination of HT and drought had the lowest leaf photosynthetic rates. Overall, HT or drought had similar effects (about 48–56 % decrease) on spikelet fertility, grain numbers and grain yield. High temperature decreased grain numbers (by 56 % averaged across both experiments) and individual grain weight (by 25 %), while, respective decreases due to drought were 48 % and 35 %. This suggests that the grain numbers were more sensitive to HT and grain weights to drought for the range of temperatures tested in this research. The interaction between HT and drought stress was significant for total dry weights, harvest index and spikelet fertility, particularly when HT stress was severe (34/22 °C). The combined effects of HT and drought were greater than additive effects of HT or drought alone for leaf chlorophyll content, grain numbers and harvest index. High temperature stress and the combination of HT and drought stress but not drought stress alone resulted in the overexpression of EF-Tu in both spring wheat cultivars.