Biological indicators can be used both to estimate ecological condition and to suggest plausible causes of ecosystem degradation across the U.S. Great Lakes coastal region. Here we use data on breeding bird, diatom, fish, invertebrate, and wetland plant communities to develop robust indicators of ecological condition of the U.S. Lake Superior coastal zone. Sites were selected as part of a larger, stratified random design for the entire U.S. Great Lakes coastal region, covering gradients of anthropogenic stress defined by over 200 stressor variables (e.g. agriculture, altered land cover, human populations, and point source pollution). A total of 89 locations in Lake Superior were sampled between 2001 and 2004 including 31 sites for stable isotope analysis of benthic macroinvertebrates, 62 sites for birds, 35 for diatoms, 32 for fish and macroinvertebrates, and 26 for wetland vegetation. A relationship between watershed disturbance metrics and 15N levels in coastal macroinvertebrates confirmed that watershed-based stressor gradients are expressed across Lake Superior's coastal ecosystems, increasing confidence in ascribing causes of biological responses to some landscape activities. Several landscape metrics in particular-agriculture, urbanization, human population density, and road density-strongly influenced the responses of indicator species assemblages. Conditions were generally good in Lake Superior, but in some areas watershed stressors produced degraded conditions that were similar to those in the southern and eastern U.S. Great Lakes. The following indicators were developed based on biotic responses to stress in Lake Superior in the context of all the Great Lakes: (1) an index of ecological condition for breeding bird communities, (2) diatom-based nutrient and solids indicators, (3) fish and macroinvertebrate indicators for coastal wetlands, and (4) a non-metric multidimensional scaling for wetland plants corresponding to a cumulative stress index. These biotic measures serve as useful indicators of the ecological condition of the Lake Superior coast; collectively, they provide a baseline assessment of selected biological conditions for the U.S. Lake Superior coastal region and prescribe a means to detect change over time.