Wallace Bryton (Justin Long) and friend Teddy Craft (Haley Joel Osment) host the popular podcast The Not-See Party, where Wallace finds videos of people doing humiliating things and shows them to Teddy while they make fun of the people on the videos. Their latest victim is the Kill Bill Kid, (Douglas Banks) who accidentally slices his right leg off with a katana. Wallace then announces his plans to fly to Canada to interview (and make fun of) him. In flashbacks spread through the film, its revealed that Wallace was originally an unpopular standup comic who became popular with his increasingly vicious podcasts, which upsets his girlfriend Ally León (Genesis Rodríguez) and leads to fights accusing him of selling out.
Upon arriving in Manitoba, Wallace learns the Kill Bill Kid has accidentally killed himself when arriving at his funeral. Upset that he's flown to Canada for nothing, Wallace decides to stay an extra day with the intention of finding another weirdo to interview. When using the restroom at a bar, he comes across a handbill from someone offering a room in his home for free and the guarantee of hearing a lifetime of interesting stories. His interest piqued, Wallace arrives at the stately home of Howard Howe (Michael Parks), an older man in a wheelchair, who offers tea and several of his interesting stories at sea. The one Howe is most passionate about telling is when one of the ships he served on crashed when looking for a legendary great white shark and how a walrus he named Mr. Tusk saved him from drowning. As Howe tells his story, Wallace passes out from drugs laced in his tea.
The next morning, Wallace wakes up to find himself strapped into a wheelchair and his left leg amputated. Howe tells him he saw a Recluse spider crawl out of his pant leg and a local doctor had to amputate it to save Wallace's life. Wallace finds the story incredulous and finally realizes Howe's insanity when he makes a joke about the spider over dinner, where Howe not only reveals his ability to walk, but his plans for Wallace: having a frightening obsession with the walrus, he plans to fit Wallace into a perfectly constructed walrus costume. His attempts to contact Ally and Teddy - having an affair behind Wallace's back - fail when neither answer their phone before Howe beats him in the back of the head with an oosik telling him his human life is over.
Now fully aware of the danger Wallace is in, Ally and Teddy fly to Canada to look for him, turning up numerous failed leads. Back at the mansion, as Howe continues to mutilate and alter Wallace, he tells his backstory as a Duplessis orphan and how years of physical, psychological and sexual abuse throughout his childhood have driven him completely mad and cemented years of hatred towards humanity. Howe's work completed, Wallace is sewn into a horrific walrus pelt made of human skin, the tusks made of the tibia bones from Wallace's severed legs. Howe revels at the return of his beloved Mr. Tusk in his monstrous aberration of man and walrus.
Local detective Frank Garmin puts Ally and Teddy in touch with Guy Lapointe (Johnny Depp), an alcoholic Quebec ex-cop who has been hunting Howe for years, once finding him by chance a few years before under a different name and living situation. He reveals that Howe, nicknamed The First Wife by the police for his horrific M.O., has been kidnapping and murdering people for years (though unaware of his walrus creations) and believes Wallace may still be alive, but not as they remember him. They eventually find Howe's address through two convenience store clerks Wallace had annoyed earlier.
As the three arrive at Howe's home, Wallace's psyche has been completely broken and conditioned to be like that of a walrus. Howe then reveals his other secret: his real obsession comes from killing and eating Mr. Tusk six months after living on the island and, out of guilt for his human qualities, has changed all these people into his beloved savior in a chance to relive their last day and give him another chance at survival. Dressed in his own homemade pelt, Howe and Wallace engage in a messy walrus fight that ends in Wallace going full walrus and killing Howe with his tusks. Ally and Teddy find the enclave and are horrified by Wallace's altered appearance. As he bellows at them like a walrus, Guy Lapointe enters and aims a shotgun at it.
One year later, Wallace, still sewn into the pelt, lives what life he has in a wildlife sanctuary. Ally and Teddy, still broken up over the situation, come visit him and feed him a mackerel. Ally, remembering a discussion she had with Wallace the day before he left for Canada about how crying separates humans from animals, tells Wallace she still loves him before walking off crying. Tears run down Wallace's face/tusks as he bellows.