Illustrating the relationship between past settlement changes and human-land could help us to understand the complex interactions among climate, human activities, and the environment. Based on archeological literature and fieldworks, this paper combines dating techniques and GIS analysis to explore the spatial and temporal distribution characteristics and human diffusion of Neolithic settlements in the Western Guanzhong Basin (WGB), and to quantitatively analyzes the relationship between human activities and natural geographic factors by index model. The results show that: (1) There was a continuity of Neolithic cultures in the WGB and the absolute chronological sequence of human activities ranges from 7500 to 3900 a BP; (2) The distribution of settlements tends to be on river terraces and Loess tableland, and with the evolution of Neolithic cultures, human activities shifted from near-water to far-water distributions and expanded to areas of high gradient. The center of activity of the settlement spreads from a single nucleus (the Wei River) to multiple nuclei (the Wei River, the Qian Rivers, and the Qishui River) and back to a single nucleus on the northern bank of the Wei River in the area of present Qishan-Fufeng, laying the foundation for the development and strength of the Western Zhou Dynasty Cultures in this area; (3) The suitability level of the natural geographic environment in the WGB gradually decreased from the Wei River to the north and south, and settlements were mainly distributed in the highly and moderately suitable zones; (4) It was found that as early as the Neolithic period, mankind had already grasped certain laws of nature, and the spatial distribution of settlements reflected mankind’s awareness of disaster avoidance and “compromise and reconciliation.”