In 2015, the Pacific marine heat wave, low river flows, and record high water temperatures in the Columbia River Basin contributed to a near-complete failure of the adult migration of endangered Snake River sockeye salmon (Oncorhynchus nerka, NOAA Fisheries 2016). These extreme weather events may become the new normal due to anthropogenic climate change, with catastrophic consequences for endangered species. Existing anthropogenic pressures may amplify vulnerability to climate change, but these potential synergies have rarely been quantified. We examined factors affecting survival of endangered sockeye (Oncorhynchus nerka) and threatened Chinook salmon (O. tshawytscha) as they migrated upstream through eight dams and reservoirs to spawning areas in the Snake River Basin. Our extensive database included histories of 17,279 individual fish that migrated since 2004. A comparison between conditions in 2015 and daily temperatures and flows in a regulated basin forced by output from global climate models showed that 2015 did have many characteristics of projected future mean conditions. To evaluate potential salmon responses, we modeled migration timing and apparent survival under historical and future climate scenarios (2040s). For Chinook salmon, adult survival from the first dam encountered to spawning grounds dropped by 4-15%, depending on the climate scenario. For sockeye, survival dropped by ~80% from their already low levels. Through sensitivity analyses, we observed that the adult sockeye migration would need to shift more than 2 weeks earlier than predicted to maintain survival rates typical of those seen during 2008-2017. Overall, the greater impacts of climate change on adult sockeye compared with adult Chinook salmon reflected differences in life history and environmental sensitivities, which were compounded for sockeye by larger effect sizes from other anthropogenic factors. Compared with Chinook, sockeye was more negatively affected by a history of juvenile transportation and by similar temperatures and flows. The largest changes in temperature and flow were projected to be upstream from the hydrosystem, where direct mitigation through hydrosystem management is not an option. Unfortunately, Snake River sockeye have likely lost much of their adaptive capacity with the loss of the wild population. Further work exploring habitat restoration or additional mitigation actions is urgently needed.