Drought is the most critical environmental stress limiting crop productivity and yield. Rice is one of the top leading food crops worldwide and modern rice varieties are notably drought-sensitive due to their high-water requirements. Generating drought-resilient varieties and fine-tuning their yield performance are time-consuming tasks that could be achieved by exploiting the genetic diversity expressed by the wild ancestors of current-day crop species. We conducted a large-scale field experiment, imposing pre-flowering and post-flowering water shortages on 20 Oryza genotypes. Using detailed agro-physiological, isotopomics, and metabolite characterization of different Asian and African rice accessions, we shed light on the evolutionary biases that have evolved into the spectrum of strategies used to adapt to drought and have added to the rice knowledge base. We find that relevant decreases in photosynthetic rates (linked with stomatal opening) that differed between genotypes. We also identified genotypic differences in core C and N metabolism, and central metabolic pathways, highlighting the possible mechanisms of drought tolerance. Additionally, data suggest strong genetic associations of several amino acids that are significantly enriched during drought. We provide strong evidence of the distinctiveness of agro-physiological and metabolic pathway behaviors to drought across the use of diverse germplasm resources. Also, the resulting data provide insight into the wide variety of germplasm responses triggered by drought.