This study investigates the evolving dynamics of economic connectedness within the Great Lakes–St. Lawrence (GLSL) region, focusing on the manufacturing sector across eight U.S. states and two Canadian provinces. Leveraging monthly manufacturing employment growth rates from January 1990 to December 2024, the analysis employs a Vector Autoregressive (VAR) model combined with Elastic Net regularization to capture the interdependencies and directional spillovers among these highly integrated regional economies. Through forecast error variance decomposition, the approach identifies the contributions of shocks originating in any given state or province to fluctuations in the others, thereby quantifying both the magnitude of influence (“Connectedness To”) and the degree of exposure (“Connectedness From”). The results reveal a complex yet discernible network of industrial linkages, with states such as Ohio and Indiana emerging as consistent net transmitters of shocks and provinces like Quebec displaying relatively lower susceptibility to external disturbances. A rolling window estimation confirms that these patterns vary over time, frequently intensifying during episodes of macroeconomic stress, such as the 2008–2009 financial crisis and the onset of the COVID-19 pandemic. The findings highlight the significance of coordinated policy interventions aimed at stabilizing key nodes in the network and underscore the importance of diversification and risk management strategies for entities that exhibit heightened exposure.