The film opens up with Kate, Humphrey and the pups, who are on their way to Alfred Creek Falls for their first family vacation together. The pups – especially Claudette – are feeling lonely for not bringing the other animals, but Kate reminds them that it’s their first vacation to share experiences. Claudette has a flashback of her and Fleet from the third film and ends up embarrassing herself in front of her family. Kate feels uncomfortable from this and Runt starts teasing Claudette for her infatuation with Fleet. Stinky suggests his plan for creating a wolf park to supervise the young wolves, but Humphrey disowns it, much to Stinky’s dismay. After this, they continue their trip but eventually come across two female wolves running to hide from human wolf trappers. The wolves inform Kate and Humphrey that the trappers are trapping wolves and wolf pups to relocate them on the other side of the country, and that all the other wolves are hiding in the mountains near the border. The two wolves are captured when they try to escape. Humphrey suggests going across the border to escape the trappers, as Kate senses the Canadian express they used before.
The wolves hide under a log in order to get across the field, only to stop in front of the trappers, who have tranquilized the two female wolves. The trappers then spot Kate, Humphrey and the pups, and a chase ensues where the wolves narrowly escape. They miss the train and realize the trappers are still on their trail. Meanwhile, Marcel and Paddy have been ordered by Winston to go and search for Kate, Humphrey and the pups. They come across Fleet, Brent and Agnes who are also looking for them. Fleet also appears to be deeply in love with Claudette and vows to save her and her family. They all agree to go on a search party. Freida and Fran show up and also join in. While the trappers are searching for the wolves, Kate, Humphrey and the pups are hiding in a tree, thanks to an idea Runt had earlier. The pups ask their parents about how they went on their first date, flashing back to the Moonlight Howl scene from the first film. Once the trappers get closer, Humphrey tells Kate to lead the pups away while he distracts the trappers. Just as one of them is about to shoot Humphrey, Brent, Fleet and the porcupines arrive just in time to help. Humphrey catches up with his family while Fleet reunites with Claudette, Runt (who has sprained his ankle) with Freida and Fran and Stinky with Brent and Agnes. The animals reach the train by nightfall and manage to get inside of one of the carts just before the trappers can capture them.
The cart turns out to be the same cart Kate and Humphrey used to get back to Jasper before, as they reminisce the first time they howled together. They are about to kiss, but Brent interrupts them, claiming he ”has to pee”. The animals help him by singing his song, and Humphrey remembers the same thing he did in the first film. When the train stops, the animals jump out and Paddy informs them that they are getting closer to the border. The next day, Stinky senses the presence of a nearby moose, which leads to a flashback showing Humphrey’s embarrassing encounter with one by Marcel flew him into a moose’s butt and farted on him as he screams well much to his shock and embarrassment. He describes he had this wide stance and had to go to counseling. The moose appears, Humphrey doesn’t recognizes him at first then the moose turns around showing his butt and then realizes it was him. Then, Stinky senses the wolf trappers getting closer. The animals cross an open field and Paddy and Marcel direct them to a nearby human road, where the trappers can’t shoot. They reach the road and narrowly avoid being shot from the plane.
As they travel on the road, Kate and Humphrey start to worry about Runt’s sprained ankle, but the trappers once again catch up to them. Just as they are about to shoot the wolves (who are hiding in a small rock den), Runt and the porcupines scare them away. The next day, the animals reach the same RV from before. They encounter Debbie, the woman who recently broke up with her boyfriend, Garn. She decides to shelter the animals for the day. The wolf trappers arrive and ask her if she has seen the wolves, but she denies it while the animals hide. When they leave, Humphrey instructs Debbie to drive them to Idaho, where the trappers won’t follow them anymore. Debbie also mentions she was planning on driving to Idaho, so she takes them there, but the wolf trappers spot them again. A car chase ensues and eventually Debbie drives in the forest to let the animals free, but the trappers catch up and follow them. Debbie notices the two female wolves from earlier in crates and frees them. Just as they reach Idaho, the wolf trappers start shooting at them, with Runt falling behind. In order to save his family, Humphrey tells Kate once again to lead the pups to safety, while he turns around and attacks the trappers.
Kate, the pups and the rest of the animals make it through the border (on the same golfing course Kate and Humphrey first met Marcel and Paddy), but Humphrey doesn’t show up. As they hear gun shots, Kate rushes back into the forest to save Humphrey, while the others wait and hope. The pups are feeling very worried for their parents, but Kate and Humphrey eventually return, unharmed. The animals finally reach Alfred Creek Falls for their vacation. The film comes to an end with all of them heading back to Jasper Park, as Humphrey starts making animal impressions.