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Oil palm ( Elaeis guineensis Jacq.) is a highly productive crop economically significant for food, cosmetics, and biofuels. Abiotic stresses such as low water availability, salt accumulation, and high temperatures severely impact oil palm growth, physiology, and yield by restricting water flux among soil, plants, and the environment. While drought stress's physiological and biochemical effects on oil palm have been extensively studied, the molecular mechanisms underlying drought stress tolerance remain unclear. Under water deficit conditions, this study investigates two commercial E. guineensis cultivars, IRHO 7001 and IRHO 2501. Water deficit adversely affected the physiology of both cultivars, with IRHO 2501 being more severely impacted. After several days of water deficit, there was a 40% reduction in photosynthetic rate ( A ) for IRHO 7001 and a 58% decrease in IRHO 2501. Further into the drought conditions, there was a 75% reduction in A for IRHO 7001 and a 91% drop in IRHO 2501. Both cultivars reacted to the drought stress conditions by closing stomata and reducing the transpiration rate. Despite these differences, no significant variations were observed between the cultivars in stomatal conductance, transpiration, or instantaneous leaf-level water use efficiency. This indicates that IRHO 7001 is more tolerant to drought stress than IRHO 2501. A differential gene expression and network analysis was conducted to elucidate the differential responses of the cultivars. The DESeq2 algorithm identified 502 differentially expressed genes (DEGs). The gene coexpression network for IRHO 7001 comprised 274 DEGs and 46 predicted HUB genes, whereas IRHO 2501's network included 249 DEGs and 3 HUB genes. RT-qPCR validation of 15 DEGs confirmed the RNA-Seq data. The transcriptomic profiles and gene coexpression network analysis revealed a set of DEGs and HUB genes associated with regulatory and transcriptional functions. Notably, the zinc finger protein ZAT11 and linoleate 13S-lipoxygenase 2-1 ( LOX2.1 ) were overexpressed in IRHO 2501 but under-expressed in IRHO 7001. Additionally, phytohormone crosstalk was identified as a central component in the response and adaptation of oil palm to drought stress.