This study analyzes the strength of inter-connections between energy, water and agriculture across the U.S. in relation to the evolution of individual sector indicators such as water scarcity, electricity demand, agricultural production and fertilizer use. Regions with strong inter-sectoral connections are those where stressors in one sector can have unforeseen impacts in the others and call for integrated management. Concepts from network theory and Input-Output (IO) analysis are used to identify and quantify key inter-sectoral linkages. The analysis is conducted at progressively finer sector-relevant scales by telescoping in from large river basins across electricity grid-regions, down to states and counties. The Global Change Analysis Model (GCAM) is combined with a suite of GCIMS software (Tethys, Demeter, Xanthos, Metis) to capture both human and earth system dynamics at the global and local scales. Results detail how inter-sectoral connections evolve across the U.S. to drive certain cross-sectoral dynamics in response to stressors in individual sectors.