Rapid population growth and subsequent urbanization pose significant challenges of water shortage in arid regions. As an important area along the One Belt and One Road line, the Northern Slope of Tianshan Mountains (NSTM) has suffered from water shortages owing to rapid urbanization in recent decades. To conserve water resources and protect the ecosystem, understanding the temporal and spatial variations of the domestic water consumption, availability, and its influencing factors is essential. According to water resource regionalization and its characteristics in NSTM, it was divided into three sections, namely the west section, the middle section, and the east section. In addition, this work characterized the temporal and spatial variation of domestic water consumption in NSTM with a focus on the understanding of the influence of urbanization on domestic water consumption from 1990 to 2020 based on three sections. The results showed that during this period of time, construction land use increased by 2256 km2 corresponding to the population increase of 158.58 × 104. Subsequently, the total domestic water consumption increased from 7.55 × 107 m3 in 1990 to 2.60 × 108 m3 in 2020. The eastern section demonstrated steady growth, while the western and middle sections experienced larger fluctuations in domestic water consumption. Urbanization has been identified as a significant factor influencing the shift in domestic water consumption. This study offers a scientific foundation for the sustainable management of water resources in arid areas.