Taking 38 third-class water resource regions of Northwest China as the study subject, the spatiotemporal evolution trend of habitat quality in Northwest China and typical third-class water resource regions from 1985 to 2023 was assessed by using InVEST model. And combined with Sen’s slope estimation method, the significance of the trend was analyzed. The XGBoost model was employed to establish quantitative relationships between habitat quality and driving factors, while the SHAP method was used to quantify the impacts of climate, human activities, and underlying surface conditions. The results showed that the overall habitat quality in the Northwest China was relatively low from 1985 to 2023, with an average habitat index of 0.428 over the years. The time showed a fluctuating trend of first decreasing, then increasing, and then decreasing again, with significant spatial differentiation. It presented a circular pattern with higher mountains in the south, north, and east and lower deserts in the central region. The differences in typical third-class water resource regions are prominent, with the habitat quality of Shiyang River, Heihe River, and Shule River showing an upward trend. In 2023, the habitat index increased by about 10.3%, 5.0%, and 2.8% respectively compared to 1985, and spatially decreased from the southern Qilian Mountains to the northern corridor plain. Ecological protection projects and increased precipitation jointly drive the improvement of habitat quality. The overall habitat quality of the Tarim River is relatively low, with an annual average change range of habitat index of 0.188-0.427. The habitat quality south of the main stream is lower than that north of the main stream. The small rivers of Hotan River and Kriya River show an upward trend, while the Aksu River and Kashgar River show a downward trend. The proportion of arable land and precipitation are the main driving factors for the regional habitat decline. The habitat quality of Ili River and Emin River is relatively high, with an average annual habitat index of 0.793 and 0.787, respectively, but the decline is significant. In 2023, the habitat index will decrease by 6% and 7.8% compared to 1985, respectively. The expansion of arable land is the main driving factor. The habitat quality of Ili River and Emin River is relatively high, with an average annual habitat index of 0.793 and 0.787, respectively, but the decline is significant. In 2023, the habitat index will decrease by 6% and 7.8% compared to 1985, respectively. The expansion of arable land is the main driving factor. The core driving factors for habitat quality in the northwest region are normalized difference vegetation index