Impoundments and diversions in freshwater corridors can alter the availability and concentration of natal water cues that migratory salmon rely on to guide homing during spawning migrations, although this has rarely been examined. By combining radiotelemetry and noninvasive biopsy, we provide the first detailed account of the effects of varying natal water concentrations, temperature, and individual physiology on the homing behaviour of wild adult Pacific salmon migrating through a regulated river. Most (89%) of the 346 sockeye salmon (Oncorhynchus nerka) from the two distinct populations tracked in this study in southwestern British Columbia (Canada) delayed their migration in the outlet of a powerhouse that discharges strong concentrations of natal lake water and subsequently wandered in the Fraser River before continuing upstream into the Seton River, where natal water cues can also vary. There were few associations between metabolic stress indices and reproductive hormone levels with this behaviour in either population; however, higher temperatures and elevated natal water concentrations in the Seton River were associated with shorter powerhouse delays and less wandering in late-run migrants.