Large-scale human activities on the Loess Plateau have caused dramatic changes in the substratum and altered the landscape pattern of the watershed, even affected the runoff production and sink processes. Based on the Budyko hydrothermal coupling equation, landscape index calculation, and regression analysis methods, this paper takes the Sanchuan River Basin in western Shanxi Province, located in the loess hilly gully area, as an example, to analyze the causes of runoff changes in the basin caused by changes in landscape patterns at different scales and to discern the influence of geographic landscape space on the production and sink processes. The results show that:(1) the runoff in the study area has decreased sharply from 1980 to the present, in which the contribution of subsurface changes to runoff was 60.81%. (2) The substrate changes from 1980 to the present caused the fragmentation and regularization of the landscape patches in the watershed, and the fragmentation and spreading of the landscape pattern increased. (3) Using a stepwise linear regression model, the landscape pattern changes in runoff reduction could be localized to specifically geographic spaces. The reduction of the core areas of woodland patches in the upper reaches of the eastern and northern tributaries and their confluence, and the disruption of the connectivity of water patches by the urban built-up areas at the confluence of the tributaries, are the direct spatial causes of the runoff reduction in watershed. An interdisciplinary approach is used to explore the potentially spatial correlation between landscape patterns and runoff changes, and to reveal the response of runoff to landscape pattern changes, which can provide a decision basis for water resources management and ecological planning on the Loess Plateau.