In a magical world, a village inhabited by small blue creatures known as Smurfs is preparing for the Blue Moon Festival. The Smurfs live happily and harmoniously under the guidance of their wise leader, Papa Smurf. However, danger looms as the evil wizard Gargamel, who has been searching for the Smurf village for years to harness their magic, finally discovers their location and chases a small group of them through the woods. In the ensuing commotion, Clumsy Smurf stumbles into a forbidden grotto and the rest of the group follows, only to find themselves sucked into a vortex that transports them to New York City.

Stranded in the bustling metropolis, the Smurfs must navigate the unfamiliar and larger-than-life world of humans as they search for a way back home before Gargamel catches them. They encounter Patrick and Grace Winslow, a soon-to-be-parent couple whose lives take an unexpected turn when they meet the Smurfs. The couple decides to help their new friends, despite the challenges and chaos their presence brings into their lives. Together, they must find a way to protect the Smurfs from Gargamel's grasp while also working to find the portal that appears with the Blue Moon and will allow them to return to their village safely.