Fonio millet is an orphan crop with great economic and food security potential. However, drought negatively affects its production and yield in semi-arid and arid regions. This study compared the growth and metabolomic profiles of two contrasting fonio accessions (NGB02089 and NGB02082) in response to water stress at the seedling stage. The results showed variation in the morph-agronomic characters of the accessions. There were also significant (p < 0.05) positive correlations in the traits studied which means that the traits can be improved simultaneously. Chlorophyll content increased progressively with weeks after sowing (WAS) but decreased when seedlings were exposed to water stress. Biomass yield of NGB02082 was higher than that of NGB02089 although the latter grew more vigorously. However, NGB02089 had longer roots. The GC-MS analysis identified 12 significant metabolites that differed in composition between the fonio accessions, including sugars, fatty acids and siloxanes. The amount of siloxane decreased in NGB02082 with increasing drought duration increased but increased in NGB02089. Similarly, cis-13-octadecenoic acid was present in NGB02082 at 4 WAS but absent at 5 WAS, whereas NGB02089 produced more metabolites. Similarly, phthalimide, triacontane, vaccenic acids, and cholestane were produced in response to drought stress duration. The results of this study showed that NGB02089 and NGB02082 have different metabolomic responses to drought, which confers resistance to NGB02089 while NGB0282 is drought susceptible. The result of this study suggests that metabolic responses to drought may be useful in developing varieties with a better tolerance or adaptation to drought conditions.