There is growing interest for using Spectral Vegetation Indices (SVI) derived by Unmanned Aerial Vehicle (UAV) imagery as a fast and cost-efficient tool for plant phenotyping. The development of such tools are of paramount importance to continue progress through plant breeding, especially in the Mediterranean basin, where climate change is expected to further increase yield uncertainty. In the present study, NDVI, SR and GNDVI derived from UAV imagery were calculated for two consecutive years in a set of twenty durum wheat varieties grown under a water limited and heat stressed environment. Statistically significant differences between genotypes were observed for SVIs. GNDVI explained more variability than NDVI and SR, when recorded at booting. GNDVI was significantly correlated with grain yield when recorded at booting and anthesis during the 1st and 2nd year, respectively, while NDVI was correlated to grain yield when recorded at booting, but only for the 1st year. These results suggest that GNDVI has a better discriminating efficiency and can be a better predictor of yield when recorded at early reproductive stages. The predictive ability of SVIs was affected by plant phenology. Correlations of grain yield with SVIs were stronger as the correlations of SVIs with heading were weaker or not significant. NDVIs recorded at the experimental site were significantly correlated with grain yield of the same set of genotypes grown in other environments. Both positive and negative correlations were observed indicating that the environmental conditions during grain filling can affect the sign of the correlations. These findings highlight the potential use of SVIs derived by UAV imagery for durum wheat phenotyping at low yielding Mediterranean conditions.