Understanding the spatial point pattern of human settlements and their geographical associations are important for understanding the drivers of land use and land cover change and the relationship between environmental and ecological processes on one hand and cultures and lifestyles on the other. In this study, a Geographic Information System (GIS) approach, Ripley’s K function and Monte Carlo simulation were used to investigate human settlement point patterns. Remotely sensed tools and regression models were employed to identify the effects of geographical determinants on settlement locations in the Wen-Tai region of eastern coastal China. Results indicated that human settlements displayed regular-random-cluster patterns from small to big scale. Most settlements located on the coastal plain presented either regular or random patterns, while those in hilly areas exhibited a clustered pattern. Moreover, clustered settlements were preferentially located at higher elevations with steeper slopes and south facing aspects than random or regular settlements. Regression showed that influences of topographic factors (elevation, slope and aspect) on settlement locations were stronger across hilly regions. This study demonstrated a new approach to analyzing the spatial patterns of human settlements from a wide geographical prospective. We argue that the spatial point patterns of settlements, in addition to the characteristics of human settlements, such as area, density and shape, should be taken into consideration in the future, and land planners and decision makers should pay more attention to city planning and management. Conceptual and methodological bridges linking settlement patterns to regional and site-specific geographical characteristics will be a key to human settlement studies and planning.