Drought is a major environmental constraint responsible for grain yield losses of bread wheat (Triticum aestivum) in many parts of the world. Progress in breeding to improve complex multigene traits, such as drought stress tolerance, has been limited by high sensitivity to environmental factors, low trait heritability, and the complexity and size of the hexaploid wheat genome. In order to obtain further insight into genetic factors that affect yield under drought, we measured the abundance of 205 metabolites in flag leaf tissue sampled from plants of 179 cv Excalibur/Kukri F1-derived doubled haploid lines of wheat grown in a field experiment that experienced terminal drought stress. Additionally, data on 29 agronomic traits that had been assessed in the same field experiment were used. A linear mixed model was used to partition and account for nongenetic and genetic sources of variation, and quantitative trait locus analysis was used to estimate the genomic positions and effects of individual quantitative trait loci. Comparison of the agronomic and metabolic trait variation uncovered novel correlations between some agronomic traits and the levels of certain primary metabolites, including metabolites with either positive or negative associations with plant maturity-related or grain yield-related traits. Our analyses demonstrate that specific regions of the wheat genome that affect agronomic traits also have distinct effects on specific combinations of metabolites. This approach proved valuable for identifying novel biomarkers for the performance of wheat under drought and could facilitate the identification of candidate genes involved in drought-related responses in bread wheat.