Drought and associated high temperatures are the major environmental stresses limiting wheat productivity in Mediterranean region. To evaluate the physiological and yield responses of durum wheat varieties under high temperature and drought stress in Mediterranean region, 15 durum wheat cultivars were grown in two consecutive years (2007-08 and 2008-09). The varieties were grown under two temperature regimes viz. normal temperature (normal sowing time) and high temperature (late sowing time), and/with two water regimes viz. rain fed (RF) and supplement irrigation (SI) conditions. Our results indicated that at rain-fed environment (water stress) caused a significant reduction in physiological parameters and grain yield. Water stress reduced 30.0 and 13.8% grain yield in 2007-08 and 2008-09, respectively. Warm environment (heat stress) caused significant reductions in physiological parameters and grain yield of 54 and 32% in 2007-08 and 2008-09, respectively. Hence, delayed sowing associated with high temperature resulted in an overall decrease in grain yield. Significant differences in grain yield was found among the varieties. Based on the growth traits and economic-yield, the cool irrigated environment is most suitable followed by the environment in cool rain-fed. However, the variety Balcah-2000 and Fuatbey-2000 achieved the highest yield under cool well-watered conditions and hence best for grown under well-watered cropping systems. Grain yield was strongly correlated with SPAD value in cool environment (RF) while, negative correlation in warm conditions (RF). On the other hand, grain yield was strongly correlated with specific leaf weight (SLW) value in cool environment (RF). A negative correlation between grain yield and flag leaf nitrogen content (FLNC) was observed under warm conditions (RF). A positive and significant correlation between SLW and FLNC was recorded under warm conditions (RF). The ash content (AC) has a positive correlation with FM in cool environment (SI). A positive and significant correlation between FLNC and SPAD under cool (SI) and warm (Rf) conditions. The chlorophyll fluorescence contributes significantly to yield stability under stressed environments. Positive correlations of chlorophyll with grain yield make it possible to evaluate genotypes with high yield stability and consequently, can be used as a selection criterion to identify the environment stress tolerance of wheat genotypes. Balcah-2000 and Solen-2002 cultivars are potentially good candidates for producing good yield in the hot and dry climates in Mediterranean conditions.