In the context of ecological civilization construction in China, interregional ancient trees are important natural and cultural resources, and it is vital that they are effectively protected and utilized according to their spatial distribution and regional conditions in order to provide a balance between local economic development and the ecological environment. This article analyzes the spatial heterogeneity of 26,842 ancient trees and explores the underlying natural and human factors by using geoinformatics–based techniques (i.e., the nearest neighbor index, kernel density, spatial autocorrelation, and the geographically weighted regression model) in Henan Province, Central China. The research findings conclude that: (1) The interregional ancient trees show positive spatial autocorrelation, and the aggregation effect in Western Henan is the most significant. (2) The growing environment and elevation exert a more obvious influence on the spatial pattern of interregional ancient trees. (3) The main influencing factors per region are different, for example, historical culture in Western Henan, water source and elevation in Southern Henan, and the growing environment in Eastern Henan, while ancient trees in Northern Henan have a weak relationship with each factor. This research facilitates political strategy making for sustainable development and the protection of interregional ancient trees.