Watersheds provide a range of services valued by society, incorporating biotic and abiotic functions within their boundaries. Recently, an operational definition of watershed integrity was applied and indices of watershed integrity (IWI) and catchment integrity (ICI) were developed and mapped for the conterminous United States. However, these indices were originally derived using equally-weighted first-order approximations of relationships between anthropogenic stressors (obtained from the U.S. EPA’s StreamCat dataset) and six watershed functions. In addition, the original calculations of the IWI and ICI did not standardize metrics across these differing scales, resulting in IWI and ICI values that are not directly comparable. We provide an example of how to iteratively update the stressor-watershed function relationships using random forest models and a nationwide response metric representative of one of the six watershed functions. Specifically, we focused on the chemical regulation function (CHEM) of IWI and ICI by relating a composite metric of chemical water quality from 1914 samples to land use metrics explicit to CHEM to refine the nature of these relationships (e.g., non-linear versus linear). The rate of nitrogen fertilizer, agricultural land use, and urban land use were found to be the three most important stressors predicting the national water quality response metric. Revision of CHEM values improved the prediction of several regional- to national-scale water quality indicators. In all cases, exponential decay curves replaced the original negative linear relationship for CHEM. Therefore, the original IWI and ICI values are probably over-estimates of the actual integrity of the Nation’s watersheds and catchments. With these revisions, we provide updated national maps of IWI and ICI. The methods outlined here can be implemented iteratively as more and better data become available for all six of the watershed functions to elevate the accuracy and applicability of these indices to various land management issues.