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Kettle Falls, located 1125 km from the mouth of the Columbia River in present-day Washington State (USA), was the second-most important salmon fishing and trading locus on that river in the early historic era. We encapsulate the late Holocene history of the fishery by deriving a summed probability distribution function (SPDF) from 50 radiocarbon ages from 13 archaeological sites within 2 km of the falls. When compared to an SPDF from 307 sites from elsewhere on the Columbia Plateau, and a null model, the Kettle Falls SPDF exhibits two phases of elevated activity at 1700-1300 cal BP and 800-500 cal BP, and an intervening lull. These phases are not related to the excavation history or differential exposure of sites to taphonomic processes, but they are concordant with episodes of glacial advance in the local mountains, which reflect hemispheric-scale changes in climate. Modern returns of summer-run Chinook salmon to the Columbia River are inversely correlated with sea-surface temperature regimes in the northeast Pacific Ocean, and we propose that the occupational history of the Kettle Falls fishery echoes long-term variations in the returns of salmon to the upper Columbia River linked to climate change.