Metabolic and physiological dynamics in wheat (Triticum spp) under different drought levels are essential for understanding plant response to drought stress. In this study, we exposed wheat plants to progressive drought at the flowering stage. Changes in primary metabolites, canopy temperature (CT), and reactive oxygen species (ROS) were evaluated at different time points: day 0 (before drought), day 2, 4, 6, 8, and 10 after cutting water supply. Results showed that accumulations of 16 amino acids, and lactic acid were largely responsible for drought response in wheat. CT increased significantly under drought, and CT depression correlates with soil moisture content (r = 0.9). ROS content increased significantly under 6.5% volumetric water content concomitant with dramatic changes in canopy temperature and metabolite profiles, and suggesting a threshold moisture content that can induce maximum plant response. These results have extended our understanding of wheat response to terminal drought, and have demonstrated that a combination of liquid chromatography-mass spectrometry metabolomics, canopy temperature measurements, and ROS assay can be an effective approach in understanding drought response and determining minimum irrigation for ultimate plant performance.