In this analysis, we examine relative contributions from climate change and river discharge regulation to changes in marine conditions in the Hudson Bay Complex using a subset of five atmospheric forcing scenarios from the Coupled Model Intercomparison Project Phase 5 (CMIP5), river discharge data from the Hydrological Predictions for the Environment (HYPE) model, both naturalized (without anthropogenic intervention) and regulated (anthropogenically controlled through diversions, dams, reservoirs), and output from the Nucleus for European Modeling of the Ocean Ice-Ocean model for the 1981–2070 time frame. Investigated in particular are spatiotemporal changes in sea surface temperature, sea ice concentration and thickness, and zonal and meridional sea ice drift in response to (i) climate change through comparison of historical (1981–2010) and future (2021–2050 and 2041–2070) simulations, (ii) regulation through comparison of historical (1981–2010) naturalized and regulated simulations, and (iii) climate change and regulation combined through comparison of future (2021–2050 and 2041–2070) naturalized and regulated simulations. Also investigated is use of the diagnostic known as e-folding time spatial distribution to monitor changes in persistence in these variables in response to changing climate and regulation impacts in the Hudson Bay Complex. Results from this analysis highlight bay-wide and regional reductions in sea ice concentration and thickness in southwest and northeast Hudson Bay in response to a changing climate, and east-west asymmetry in sea ice drift response in support of past studies. Regulation is also shown to amplify or suppress the climate change signal. Specifically, regulation amplifies sea surface temperatures from April to August, suppresses sea ice loss by approximately 30% in March, contributes to enhanced sea ice drift speed by approximately 30%, and reduces meridional circulation by approximately 20% in January due to enhanced zonal drift. Results further suggest that the offshore impacts of regulation are amplified in a changing climate.