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In Skagway in the Yukon, in 1900 during the gold rush, prospector Jack Thornton plans to return to his hometown of Chicago but loses all his money in a card game.  "Shorty" Hoolihan, a New Yorker just released from jail after a six-month sentence for tampering with the mail, tells Jack about a letter he read that was sent by an ill prospector, Martin Blake, just before he died to his son John in San Francisco, which contained a map showing the location of a gold mine.  Shorty has drawn the map from memory, and although he concedes that it may be faulty in spots, he talks Jack into becoming his partner after telling him that John Blake and his wife left Skagway that day in search of the mine.

While buying a dog team, Jack and Shorty encounter a wealthy, sadistic English prospector, Mr.  Smith, who wants to buy an untamed St.  Bernard named Buck, so that he could shoot him.  Jack, who admires the dog, buys him instead, and although Buck runs away once he is freed on the trail, he returns at night in the whirling snow and curls up beside Jack.  After they come across Blake's wife Claire surrounded by wolves, she explains that Blake has been gone two days searching for food.  Believing that Blake is dead, Jack forces Claire to come with them to Dawson.

He and Claire grow fond of each other on the trail, and at Dawson, Claire agrees to become partners with them to find the gold.  Although they need money to buy an outfit, Jack, after having lost most of their provisions crossing a river, refuses to sell Buck to Smith; however, after Jack gets drunk and brags that Buck can pull a sled loaded with 1,000 pounds 100 yards, Smith wagers $1,000 against Buck that he cannot.  Jack accepts and Buck barely succeeds before he collapses in Jack's arms.

As they leave Dawson, Blake, unknown to them, is brought in barely alive.  At night, Jack pensively stares at Claire by the fire and explains his acceptance of the "Law of the Klondike"—if there is something you need, you grab it—which Claire does not accept.  Soon they find the gold, and Shorty is sent to file a claim.  As the winter approaches, Buck is tempted by the call of nearby wolves, while Jack and Claire, alone in an isolated cabin, acknowledge and consummate their love.

Meanwhile, Blake leads Smith to the gold.  When they find the cabin, Smith orders one of his men to knock out Blake.  Smith then takes the gold from Jack and Claire at gunpoint but dies with his men when their canoe overturns in rapids and the gold weights them down.  After Buck finds Blake, Jack carries him to the cabin, where he and Claire nurse him to health.  Although Jack tells Claire that he is keeping her, he relents after she explains that although she loves him, Blake needs her and that she lives by a different law than Jack.  After the Blakes leave, Buck joins the wolves and becomes a father, and Jack is left alone for the winter, but in the spring, Shorty returns with an Indian woman, whom he won in a crap game, to be their cook.