The Ili River Basin (IRB) is located in the northwest of China. With its large-scale zone and abundant resources, it is believed to be a “wet island” and a biotic resource storehouse in the dry regions of Eurasia. The IRB has stable ecological conditions and abundant water resources, providing natural conditions for agricultural production and human settlements. With the population increasing and economic development advancing, the competition for land resources is becoming fierce, leading to some ecological problems in this region. Therefore, understanding the spatiotemporal changes and driving mechanisms of the “three-zone space” (TZS) in the IRB is of significant practical importance for promoting sustainable development and optimizing the territorial spatial pattern. This study first analyzes the characteristics and intensity of the TZS changes from 2000 to 2020. Then, it utilizes the optimized parameter Geodetector (OPGD) to analyze the driving mechanisms behind these changes. The results show the following. Firstly, the agricultural space (AS) increased by a total of 837.5 km2, the urban space (US) increased by 519.64 km2, and other ecological space (OES) increased by 1518.83 km2. Green ecological space (GES) decreased by 2875.97 km2. Secondly, intensity analysis indicated that the total TZS change in IRB was 11.07%. At the spatial-type level, the increased intensities of OES, US, and AS were active. In spatial transformation intensity, US and OES tended to transform into AS; AS tended to transform into US; and OES and GES had a mutual transformation tendency. Thirdly, AS converted into US around emerging cities like Khorgas and Cocodala. The conversion towards GES was scattered. The mutual conversion between OES and GES showed spatial distribution consistency, mainly occurring in the Borohoro ranges and the Halik ranges. Lastly, regarding the driving mechanisms, the evolution of US in the IRB was driven by social and economic factors. Location and climate factors accelerated agricultural development, facilitating the transformation of GES and OES into AS. Climate and economic factors played a crucial role in the scale of conversions between OES and GES. The findings can provide a basis for the governance and protection of the IRB, help to form a rational territorial spatial pattern, and offer scientific guidance for sustainable land management.