Abstract: Populus euphratica Oliv., an established species in the Tarim Desert Area, was used to investigate variations in osmoregulatory substances and antioxidant enzyme activities of three typical heteromorphic leaves along the groundwater depth (GWD) gradient as well as differences in their adaptive strategies to drought stress. Results showed that: (1) with the increase in GWD, the relative water content, leaf water potential, soluble protein (SP) content, and peroxidase (POD) activity of the three heteromorphic leaves of P. euphratica showed a decreasing trend, while the water saturation deficit, free proline (Pro) content, soluble sugar (SS) content, and malondialdehyde (MDA) content showed an increasing trend, and superoxide dismutase (SOD) maintained high and stable activity. (2) The Pro and SS contents in lanceolate leaves showed a highly significant positive correlation with GWD, the SS and SP contents in oval leaves showed a significant positive correlation with GWD, and the SS content in serrated broad-oval leaves showed a highly significant positive correlation with GWD. (3) The lanceolate leaves maintained cellular osmotic potential through the synergistic action of Pro and SS to cope with water stress, oval leaves enhanced drought resistance through osmotic adjustment (SP, Pro, SS), and serrated broad-oval leaves maintained cellular expansion pressure with SS and Pro, while eliminating reactive oxygen species (ROS) through POD and SOD, which synergistically adapted to increasingly arid desert environments.