Dissection of the genetic basis of the adaptive response of durum wheat to unfavourable water and temperature regimes is an important prerequisite for the selection of genotypes less vulnerable to environmental constraints. An elite durum population of 249 recombinant inbred lines was tested across 16 Mediterranean environments characterised by contrasting thermo-pluviometric conditions and, consequently, a broad range of productivity (from 0.56 to 5.88 t  ha^–1). Among the environmental variables investigated, soil moisture during grain filling showed the most consistent correlation with yield components and grain yield, whereas a weaker, albeit in some cases significant, association was noted with temperature at heading and thermal time during grain filling. Ear peduncle length appeared as a valid and easy-to-phenotype morphological proxy for the water available to the plant. In total, 76 quantitative trait loci (QTLs) were identified for yield components and for several morpho-physiological traits (peduncle length, the spectral reflectance index NDVI and leaf greenness at the milk-grain stage expressed in SPAD units) associated with the adaptive response of wheat to water and heat stresses. Although most of the QTLs were significant in only one or two environments, two major QTLs on chromosomes 2BL and 3BS showed consistent additive and epistatic effects on 1000-kernel weight, peduncle length, SPAD values and grain yield in half of the environments. In view of their strong phenotypic effects on kernel weight, these two QTLs are good candidates for positional cloning in order to gain a better understanding of the functional basis of their effect on the plasticity of grain weight and grain yield.