ROMS, a high-resolution regional ocean model, was used to study how climate change may affect the northwestern Atlantic Ocean. A control (CTRL) simulation was conducted for the recent past (1976–2005), and simulations with additional forcing at the surface and lateral boundaries, obtained from three different global climate models (GCMs) using the RCP8.5 scenario, were conducted to represent the future (2070–99). The climate change response was obtained from the difference between the CTRL and each of the three future simulations. All three ROMS simulations indicated large increases in sea surface temperatures (SSTs) over most of the domain except off the eastern U.S. seaboard resulting from weakening of the Gulf Stream. There are also substantial intermodel differences in the response, including a southward shift of the Gulf Stream in one simulation and a slight northward shift in the other two, with corresponding changes in eddy activity. The depth of maximum warming varied among the three simulations, resulting in differences in the bottom temperature response in coastal regions, including the Gulf of Maine and the West Florida Shelf. The surface salinity decreased in the northern part of the domain and increased in the south in all three experiments, although the freshening extended much farther south in one ROMS simulation relative to the other two, and also relative to the GCM that provided the large-scale forcing. Thus, while high resolution allows for a better representation of currents and bathymetry, the response to climate change can vary considerably depending on the large-scale forcing.