In the small town of Wolf Lake, things are seldom what they seem. Behind the peaceful veneer of this sleepy Pacific Northwest town lies a secret hidden from the outside world for hundreds of years. This secret has formed the backbone of the town's existence, yet it remains unknown to many people who live in the community it most affects. The secret has infiltrated every aspect of the townspeople's lives, with sometimes dangerous and deadly results. That secret is about to surface in a manner that will change the fate of everyone involved for years to come.

Wolf Lake's secret lies in the ability of some of its denizens to shapeshift — to physically transform from humans into wolves. This ability has created an insular, secretive community that has remained undisturbed for centuries. But all of that is about to change, as the arrival of an outsider and a power struggle within the wolf pack together threaten to turn the clandestine society upside-down.

The outsider who is exposing the town's long-standing mystery is John Kanin (Lou Diamond Phillips), a Seattle cop who lives for two things: his work and his girlfriend, Ruby (Mia Kirshner). When Ruby mysteriously disappears, Kanin's search leads him to the secluded town of Wolf Lake, where further intrigue awaits him.

In the sheltered community, Kanin encounters a population that is in the midst of an upheaval. Sheriff Matthew Donner (Tim Matheson) is responsible for keeping the town safe, though he struggles to strike a balance between his commitment to justice and his reluctance to face the reality of his lupine nature. Further complicating matters for Donner is the budding relationship between his 16-year-old daughter Sophia (Mary Elizabeth Winstead) and Luke Cates (Paul Wasilewski), the son of the town's most powerful and respected industrialist, Willard Cates (Bruce McGill).

While Sheriff Donner has conflicted feelings about his ability to shapeshift, Willard Cates has pushed his power to its limits and rules the town — he is the Alpha Male, the leader of the the so-called "pack." But Cates's power is about to be tested by a real-estate developer named Tyler Creed (Scott Bairstow), whose ambition sparks a battle for supremacy among the shapeshifters. Further adding to the tension is the fact that Vivian ("V") Cates (Sharon Lawrence), wife of Willard and the town's resident Alpha Female, has eyes for Tyler Creed.

As the town's numerous conflicts intertwine and lead Kanin closer to the truth about Ruby Cates' disappearance, Sheriff Donner's inner struggle and the shifting balance of power in the town, one man seems to have all the answers: Sherman Blackstone (Graham Greene), a high-school biology teacher, is a mischievous, spiritual man who seems to know everyone's destiny.