Managers are often inadequately informed to make decisions for municipal watersheds, in which sources of impairment are shifting due to the combined influences of land use change, rapid ongoing human population growth, and changing environmental conditions. To progressively pursue best-managed, science-based futures, municipal watersheds can be studied using an experimental watershed approach. To demonstrate this approach in a contemporary watershed, a nested-scale experimental watershed study design was implemented in a representative, mixed-use watershed located in the Midwestern USA. Results to date show that urban/suburban development and agriculture are primary (often combined) drivers of alterations to watershed hydrology, streamflow regimes, transport of multiple water quality constituents, and stream physical habitat. However, several natural processes and watershed characteristics, such as surficial geology and stream system evolution, are likely compounding observed water quality impairment and aquatic habitat degradation. Given the varied and complicated set of factors contributing to issues in the study watershed, watershed restoration is likely subject to physical limitations and should be conceptualized in the context of achievable goals/objectives. Results demonstrate the capacity of the experimental watershed approach to objectively identify causal factors, target critical source areas, and provide the science-based information, and shared data, necessary to make effective, collaborative, and adaptive management decisions. Results further demonstrate the immense, globally transferable value of the experimental watershed approach to address municipal watershed management challenges.