Study region: Tarim River Basin (TRB) in the arid northwestern China. Study focus: The TRB is facing escalating tensions among water, energy, food, and the ecological environment (WEFE). This study developed a WEFE evaluation system using an integrated single index quantification-multiple index synthesis-multiple criteria integration approach combined with coupling coordination model to assess the spatial-temporal evolution of WEFE nexus from 2000 to 2020. The obstacle degree model and geographic detector method were applied to reveal the internal and external drivers of these changes. New hydrological insights for the region: The comprehensive development levels of WEFE and its all subsystems indicated an upward trend, with Bayingolin having the highest development level at 0.57. The WEFE coordination level steadily increased but remained at the primary coordination level. Bayingolin has the highest coordination level (0.74), whereas Kashgar exhibited the lowest level at 0.6. Energy production and agricultural water consumption ratio stood out as key internal factors affecting WEFE coordination, with obstacle values of 0.21 and 0.16, respectively. The impacts of external factors like GDP per capita, urbanization level, total regional population and rural disposable income per capita on the WEFE coordination level was increasing. These findings will facilitate to decision-making for the synergistic development of WEFE in the TRB, and hold significant reference value for other arid and water-scarce regions.