Information about what ecological conditions are likely, causes or drivers of degradation, and potential management actions to restore degraded lands may support land conservation and restoration decisions. State-and-transition models (STMs) describe persistent plant and ecological conditions that are possible (the “state”) within a given abiotic setting and drivers or actions that can cause shifts between states (the “transitions”). These primarily conceptual models are widely used to inform resource and conservation decisions. Data-driven STMs have been developed for some lands, but not at regional or national scales. Here, we demonstrate a new repeatable workflow for developing data-driven STMs in the United States (US). The approach leverages predictive maps of Ecological Site Groups (ESGs), extensive field-based Federal monitoring databases, information from Ecological Site Description (ESD) STMs, soil erosion models, remotely sensed productivity, and other available spatial information (fire, land protection, and drought) to provide context and descriptions of the data-driven states, including likely drivers of transitions. Results of this workflow applied to one dryland ESG in the Upper Colorado River Basin in the southwestern US suggest that an Invaded state (16% of 1352 plots) and some occurrences of a Grassland state (30% of plots) are in a degraded or at-risk condition with reduced ecosystem services. The most common drivers of state transitions in the associated ESDs (n = 26) are related to livestock grazing and fire. The Invaded state in the ESG has evidence of degraded habitat quality and accelerated run-off while the Grassland state occurrences show reduced richness, productivity, and elevated erosion risk by wind. Areas subject to wildfire and with lower protection status had greater probability of Invaded state occurrence, generally supporting drivers in ESDs. The workflow presented here can serve as a template for describing ecological dynamics at regional scales, and support prioritization of land for conservation and climate adaptation activities.