Ecological monitoring of streams has often focused on assessing the biotic integrity of individual benthic macroinvertebrate (BMI) communities through local measures of diversity, such as taxonomic or functional richness. However, as individual BMI communities are frequently linked by a variety of ecological processes at a regional scale, there is a need to assess biotic integrity of groups of communities at the scale of watersheds. Using 4,619 sampled communities of streambed BMIs, we investigate this question using co‐occurrence networks generated from groups of communities selected within California watersheds under different levels of stress due to upstream land use. Building on a number of arguments in theoretical ecology and network theory, we propose a framework for the assessment of the biotic integrity of watershed‐scale groupings of BMI communities using measures of their co‐occurrence network topology. We found significant correlations between stress, as described by a mean measure of upstream land use within a watershed, and topological measures of co‐occurrence networks such as network size (r = −.81, p < 10–4), connectance (r = .31, p < 10–4), mean co‐occurrence strength (r = .25, p < 10–4), degree heterogeneity (r = −.10, p < 10–4), and modularity (r = .11, p < 10–4). Using these five topological measures, we constructed a linear model of biotic integrity, here a composite of taxonomic and functional diversity known as the California Stream Condition Index, of groups of BMI communities within a watershed. This model can account for 66% of among‐watershed variation in the mean biotic integrity of communities. These observations imply a role for co‐occurrence networks in assessing the current status of biotic integrity for BMI communities, as well as their potential use in assessing other ecological communities.