The transformation of surface landscapes by human activities is the main driving factor that affects changes in ecosystem functions and ecological processes, significantly influencing the ability of regional water ecosystems to deliver products and services to human society. However, the relationship between landscape heterogeneity and multiple water ecosystem services and the mechanisms of dynamic change remain unclear, posing challenges for managing and enhancing ecosystem services through landscape management decisions. Taking the Zishui basin as an example, this study aimed to clarify the impact of landscape heterogeneity on water-related ecosystem services and relationships by analyzing the relative importance and comprehensive impacts of landscape structure composition and landscape spatial configuration changes on three ecosystem services (water production, soil conservation, and water purification). These services were quantified for the years 2000, 2005, 2010, 2015, and 2018 using the InVEST model. Furthermore, quantitative indices were constructed to assess the impact of landscape heterogeneity on water ecosystem services. The results show that annual water yield and soil conservation increased at first and then decreased from 2000 to 2018, with 24.48% and 22.50% overall decreases, respectively. In contrast, the total export of N and P decreased at first and then increased, with 3.65% and 5.18% overall increases, respectively. The contribution indices of landscape pattern changes to water yield, soil conservation, nitrogen export, and phosphorus export were 0.04%–2.02%, 0.08 × 10−2%–0.32 × 10−2%, 13.57%–70.05%, and 11.01%–68.22%, respectively, showing interannual and spatial differences. The impact of landscape pattern change on water-related ecosystem services mainly reflects intensity change, which does not change the dominant relationships. Both landscape composition and configuration have impacts on water-related ecosystem services, but the effects of composition are larger than those of configuration. Among them, the proportions of cultivated land, woodland, and construction land, along with changes in Shannon’s diversity index (SHDI), patch density (PD), and edge density (ED) have obvious influences on water-related ecosystem services and show nonlinear relationships. In summary, the impacts of landscape heterogeneity indicators on water-related ecosystem services have obvious category differences, interannual changes, and spatial differences. This study provides new insight into the driving effects of landscape pattern change on the supply of water-related ecosystem services and will provide a reference for practical land management applications and policy formulation of water ecosystem services.