With its headwaters in the water towers of the western Cordillera of North America, the Fraser River is one of the continent’s mightiest rivers by annual flows, supplies vital freshwater resources to populous downstream locations, and sustains the world’s largest stocks of sockeye salmon along with four other salmon species. Here we show the Variable Infiltration Capacity (VIC) model’s ability to reproduce accurately observed trends in daily streamflow for the Fraser River’s main stem and six of its major tributaries over 1949-2006 when air temperatures rose by 1.4 °C while annual precipitation amounts remained stable. Rapidly declining mountain snowpacks and earlier melt onsets result in a 10-day advance of the Fraser River’s spring freshet with subsequent reductions in summer flows when up-river salmon migrations occur. Identification of the sub-basins driving the Fraser River’s most significant changes provides a measure of seasonal predictability of future floods or droughts in a changing climate.