Understanding how oceanographic factors independently and interactively influence fish behavior, physiology, and survival is essential for predicting the impact of climate change on fish. Such predictions are especially challenging for highly migratory species such as salmon that experience a broad range of conditions. We applied a novel modeling approach that combines an individual-based particle model with a bioenergetics model to evaluate the effects of oceanographic variability on migration of post-smolt Atlantic salmon (Salmo salar). Interannual variability in the surface current velocity and sea surface temperature differentially influenced post-smolt salmon migration. The magnitude, duration, and direction of the currents relative to a fish's intended swimming direction had the strongest influence on migration. Changes in ocean circulation led to changes in currents at a regional scale that have a similar, relative effect across multiple populations during out-migration. Results of this study suggest that the Nova Scotia Coastal Current has a strong influence on the migration pathways of migrating salmon through the Gulf of Maine. The influx of cool fresh water from the Arctic, observed in the early 1990s, changed the Nova Scotia Coastal Current and, as suggested by model results, could have dramatically influenced post-smolt salmon migration success. There was a trade-off between arriving at the destination quickly but at a small size and not arriving at the destination at all. Fish that took a long time to migrate had more opportunities to feed and encountered warmer summer waters, increasing their overall growth.