Plants known as obligate aerobes developed different mechanisms to overcome the damage incurred under oxygen limitation. One of the survival strategies to have commonly appeared in hydrophytic plants is the escape strategy, which accelerates plant axial organs’ growth in order to escape hypoxic conditions as soon as possible. The present study aimed to distinguish the alterations in coleoptile elongation, viability and metabolic profiles in coleoptiles of slow- and fast-growing rice varieties. All the parameters were tested at 3, 5 and 7 days after sowing, to highlight changes during seedling development in normal and submerged conditions. The obtained results indicated that coleoptile elongation correlated with higher resistance to oxygen deprivation. GS-MS-based metabolic profiling indicated that coleoptiles of the fast-growing cultivar accumulated higher amounts of sugar phosphates, disaccharides, fatty acid derivatives and sterols, which are important for maintaining growth, membrane stability and viability. The slow-growing variety was characterized by a greater abundance of carboxylates, including lactate and phosphoric acid, indicating an energy crisis and cytosol acidification, leading to cell damage and low tolerance. Therefore, a metabolomics approach could be used for phenotyping (chemotyping) in the large-scale screening of newly developed varieties with higher tolerance to oxygen deprivation.