11 years after the events of the first film, Dr. Arthur Neuman is giving a tour of the hall of Norse mythology in Edge City Museum. Dr. Neuman mentions that Loki created the mask and unleashed it on Earth, and that those who wear the mask would have the powers of Loki. When Dr. Neuman mentions that Loki was imprisoned by Odin, a man in black becomes very angry and transforms, revealing himself to be Loki. The tourists panic and flee, but Dr. Neuman stays to argue with the angry god. Loki takes the mask on display, but realizes it is a fake. In anger, he removes Dr. Neuman's still talking face from his body and puts it on the mask stand, before getting rid of the guards and storming out of the museum in a whirlwind of the real mask makes its way to a town called Fringe City, and is found in a river by a dog named Otis - who belongs to Tim Avery, an aspiring animator at an animation studio, who is feeling reluctant to become a father. He has a beautiful wife, Tonya, and a best friend, Jorge. On a tropical island, Loki is relaxing until Odin confronts him and orders his son to find the mask, as it has caused too much trouble for mankind. Loki asks Odin to help him, but Odin tells Loki that this is his mess and he has to clean it up. Later that night, Tim puts on the mask for a Halloween party, transforming into an eccentric, green-faced party animal. When the company party turns out to be a bore, Tim uses his powers to perform a remix of "Can't Take My Eyes Off You", making the party a success, and giving Tim's boss the idea to turn Tim's costumed persona into a cartoon, resulting in his promotion the next returns to his house and, while still wearing the mask, conceives a baby. The baby, named Alvey, is born with the same powers as the mask, which alerts Odin. Possessing a store clerk, Odin tells Loki about this and tells him that if he finds the child, he will find the mask. Later, Tonya goes on a business trip, leaving Tim with the baby. Tim, who has been promoted at work, desperately tries to work on his cartoon at home, but is continuously disrupted by baby Alvey. In order to get some peace and quiet, Tim lets Alvey watch Michigan J. Frog, Woody Woodpecker, The Flintstones, and Transformers on the television. Alvey devilishly obtains the idea to mess with his father's head by using his powers. Meanwhile, Otis the dog, who has been feeling neglected by Tim because of Alvey, dons the mask by accident and becomes a crazed animal version of himself, who wishes to get rid of the baby, but all his attempts are overturned by Alvey. Eventually, Loki finds the mask-born baby, and confronts Tim for the mask back, but Alvey uses his powers to protect his father. Odin, possessing Tim's body, becomes fed up with Loki's destructive approach for defying him once again and strips his son of his powers. Tim is later fired after failing to impress his boss during a pitch, but is able to reconcile and bond with Alvey. Loki, still determined to please his father, manages to complete a summoning ritual and appeal to Odin to restore his powers. Odin agrees, but only for a limited time, stating this as his last chance. Loki then kidnaps Alvey to exchange for the mask. When Tonya returns home, she goes with Tim and Otis, whom Tim had apologized for ignoring him earlier and had convinced Otis that Alvey could be his new best friend, to make the exchange with Loki, but Loki decides to keep Alvey despite the exchange, causing Tim, Tonya and Otis to chase after them, as well as forcing Tim to don the mask again to fight Loki. The subsequent confrontation is relatively evenly matched due to both of them possessing equal powers, prompting Loki to halt the fight, and suggest that they let Alvey decide who he wants to live with. Although Loki tries to lure Alvey to him with toys and promises of fun, Tim wins by removing the mask and asks Alvey to come back to him using the human connection he has forged with his son, causing Alvey to choose and enraged, Loki tries to kill Tim, but his time has run out and Odin appears in person, scolding Loki for his failure and preparing to banish him. Tim, however, feels sorry for Loki and reminds Odin that regardless of their problems, they are still father and son and that "the most important thing in life is a relationship with your family". Touched by Tim's heartfelt speech, Odin reconciles with Loki as a son, and Tim gives the mask to Odin, who returns to Asgard with Loki. In the end, Tim's subsequent cartoon, based on his own experiences of Alvey and Otis competing for his attention, becomes a success and Tonya reveals that she is pregnant again.

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