Winnie the Pooh and company embark on a quest to rescue Christopher Robin from certain doom in a place called "Skull" after misreading a note he left for them.
Winnie the Pooh and Christopher Robin are best friends who wish they could be together forever. However Christopher Robin needs to go to school. Christopher Robin has trouble telling Pooh that they will be separated, so he leaves him a note. Pooh, misunderstanding and believing that Christopher Robin has gone to Skull and needs his help launches a rescue mission with the help of Rabbit, Tigger, and Piglet.
- On the last day of summer, Christopher Robin is unable to tell his friend Winnie-the-Pooh some sad news, and leaves him with the advice, "You're braver than you believe, and stronger than you seem, and smarter than you think," but Pooh does not clearly understand. The next morning, Pooh discovers a honey pot with an attached note-however, he cannot read it himself after getting honey all over it. He goes around to his friends Piglet, Tigger, Rabbit and Eeyore, but none of them are able to read the note, so they ask Owl for help. From misinterpreting the note and his own romantic imagination of adventure, Owl deduces that Christopher Robin has been taken to a distant, mysterious and dangerous place called "Skull" against his will, to a cave where the monstrous "Skullasaurus" resides. Owl equips the group with a map and sends them into the "Great Unknown" of the Hundred Acre Wood.
During their journey through the Great Unknown, as they are seemingly hunted by the Skullasaurus, the group slowly begins to realize just how helpless they are without Christopher Robin in the outside world. Piglet, Tigger, and Rabbit come to believe they do not have the courage, strength, or intelligence respectively to go on; Piglet is abducted by a swarm of butterflies in a tranquil field, leaving him feeling scared and helpless, Tigger plummets into a deep gorge and is unable to bounce out to safety, causing his friends to fall with him, and Rabbit continuously makes poor leadership decisions following Owl's inaccurate map. Pooh tries to comfort them each with the advice Christopher Robin had given him, but fails due to his inability to remember what he said. When Rabbit finally breaks down, admitting he has no idea where they are going, the group comes to terms with the fact that they are lost and helpless without Christopher Robin, and take shelter in a nearby cave. While everyone is asleep, Pooh laments on getting no closer to finding Christopher Robin.
The next morning, the five friends realize they had spent the night in the Skull Cave. The group enters and splits up to find Christopher Robin, and though Rabbit, Tigger, Eeyore, and Piglet eventually reunite, they are scared away by Pooh's distorted reflection as he walks towards them from behind a crystal wall, mistaking him for the Skullasaurus. Pooh slides down and gets stuck in a small gap in the cave's crystals, and the four others find the "Eye of the Skull" where Christopher Robin supposedly is trapped. Believing Pooh to have been eaten alive by the Skullasaurus, they rise past their fears and doubts and make their way to the Eye of the Skull. Upon seeing his friends' bravery, Pooh excitedly frees himself from the crevasse, only to slide down a rock and be trapped in a deep pit where he is unable to find a way out. While there, he realizes that Christopher Robin is still with him in his heart, even when they are not together, just as Christopher had promised. After Piglet, Rabbit, Tigger and Eeyore enter the Eye, they are found by Christopher Robin who has been searching for them as well. He reveals that he was only at school, and the roars of the Skullasaurus they have been plagued by are actually the noises of Pooh's tummy rumbling.
After Christopher Robin rescues Pooh from the pit, the six exit the Skull Cave, only to discover that from the outside, it and all the other locations on the map were not nearly as big, nor as scary as they seemed. They return home, and that evening, Christopher Robin says he will return to school the next day. Pooh declares that he will always be waiting for him, and the two happily watch the sunset, knowing they will always have each other in the sanctuary of the Hundred Acre Wood.