River ecological health assessments are the premise for protecting river biodiversity and curbing river water environment deterioration. To explore the river ecosystem health status and its response mechanism to water environmental factors in the middle reaches of the Yarlung Zangbo River, phytoplankton samples were collected during July and October 2021, and water environmental factors were measured. The phytoplankton species were identified, and their cell abundance and biomass were calculated. The phytoplankton integrity index was constructed to evaluate the ecological health status of the river. The temporal and spatial distribution characteristics of water environmental factors and phytoplankton community, as well as the correlation between P-IBI value and community parameters and water environmental factors were analyzed. The results showed that the difference in water environmental factors was not evident in time but was significant in space. The average cell abundance and biomass of phytoplankton were in the order of wet season>dry season and main stream>tributaries. Diatoms dominated the community, and pH and WT were the major water environmental factors driving the spatial and temporal distributions of phytoplankton. The ecological health status of the middle reaches of the Yarlung Zangbo River was "healthy to sub-healthy." The river health status was better than that of the dry season, and that of the tributaries was better than that of the main stream. EC, TUR, WT, NO3--N, and NH4+-N were the major water environmental factors affecting the ecological health status of the river reach, which could be affected by the direction and rate of phytoplankton community succession. It is involved in and affects the process of material circulation and energy flow of the river ecosystem, thereby driving the ecological health of the middle reaches of the Yarlung Zangbo River.