Drought stress is the main limiting plant growth factor in arid and semiarid regions. The Lanzhou lily (Lilium davidii var. unicolor) is the only sweet-tasting lily grown in these regions of China that offers highly edible, medicinal, health, and ornamental value. The Tresor lily is an ornamental flower known for its strong resistance. Plants were grown under three different drought intensity treatments, namely, being watered at intervals of 5, 15, and 25 d (either throughout the study or during specific growth stages). We measured the biomass, leaf area, photosynthetic response, chlorophyll content (SPAD value), and osmoregulation of both the Lanzhou lily and the Tresor lily (Lilium ‘Tresor'). Additionally, we employed RNA sequencing (RNA-Seq) and qRT-PCR to investigate transcriptomic changes of the Lanzhou lily in response to drought stress. Results showed that under drought stress, the decreasing rate in the Lanzhou lily bulb weight was lower than the corresponding Tresor lily bulb rate; the net photosynthetic rate, transpiration rate, and stomatal conductance of the Lanzhou lily were all higher compared to the Tresor lily; osmoregulation constituents, such as glucose, fructose, sucrose, trehalose, and soluble sugar, in the Lanzhou lily were comparatively higher; PYL, NCED, and ERS genes were significantly expressed in the Lanzhou lily. Under moderate drought, the biosynthesis of flavonoids, circadian rhythms, and the tryptophan metabolism pathway of the Lanzhou lily were all significant. Under severe drought stress, fatty acid elongation, photosynthetic antenna protein, plant hormone signal transduction, flavone and flavonol biosynthesis, and the carotenoid biosynthesis pathway were all significant. The Lanzhou lily adapted to drought stress by coordinating its organs and the unique role of its bulb, regulating photosynthesis, increasing osmolyte content, activating circadian rhythms, signal transduction, fatty acid elongation metabolism, and phenylalanine and flavonoid metabolic pathways, which may collectively be the main adaptation strategy and mechanisms used by the Lanzhou lily under drought stress.