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Rapids in the Yukon River have always focused human activity. Klik-has rapids impeded salmon migrating upstream to spawn in summer. (Klik-has means 'very bad' in the local First Nations language.) First Nations people speared salmon in the rapids and set their nets in the eddies below the rapids. Their seasonal camps were located downstream of the rapids. 

Miles Canyon and Whitehorse rapids were dangerous and famous obstacles to Gold Rush stampeders bound for the Klondike goldfields. To bypass these rapids, cargo was carried in horse-drawn carts on wooden rails, or 'tramlines', between transfer points at Canyon City and White Horse City. When the White Pass and Yukon Railway from Skagway was completed in 1900, a larger town (now Whitehorse) sprang up across the river around wharves where freight was transferred from rail cars to sternwheelers.

The Whitehorse Rapids Generating Facility, built in 1957, supplies a major part of the Yukon Territory's electricity needs. This is where the gradient of the Yukon River is steepest, providing the 'head' for hydroelectric power generation. Water falls 18 m from the dam to spin the turbines, creating electricity.  Another reason for building the dam at Whitehorse Rapids was that the basaltic lava flows that form the river banks provided an excellent foundation. Behind the dam, the Yukon River backed up to create Schwatka Lake, which in turn tamed the swift water at Miles Canyon.

The head of the Yukon River, at Chilkoot Pass, is within sight of the Pacific Ocean - yet the river does not drain into the Pacific, but rather flows more than 3000 km to the Bering Sea. The present drainage pattern of the Yukon River is a relatively recent development. Many valleys and river terraces slope to the south, and geologists believe that much of the Yukon Territory may have once drained southwestward to the Gulf of Alaska. This drainage was blocked by glaciers during the Ice Ages, and waters in central Yukon Territory were forced to find a new and much longer route through the ice-free terrain of Alaska to the Bering Sea.