Two years have passed since the events of the first film, and on Smurfette's birthday, the Smurfs gather to recount the tale of her creation. Originally intended by Gargamel to destroy the Smurfs, she was saved and transformed into a genuine blue Smurf by Papa Smurf. However, Smurfette is haunted by her origins, leading her to question her identity. Meanwhile, the Smurfs are secretly planning a birthday surprise for her, which inadvertently gives Smurfette the impression that they have forgotten her special day.
In the meantime, in Paris, Gargamel and his companion Azrael have gained fame as magicians, showcasing Gargamel's sorcery. Yet, he finds himself running low on the essential Smurf essence that fuels his magic. To counter this, he has invented two evil Smurf-like creatures dubbed the Naughties, known as Vexy and Hackus. Utilizing the Eiffel Tower as a magical conduit, Gargamel creates a portal to the Smurf Village, aiming to capture Smurfette and uncover Papa's secret formula for creating Smurfs. However, Gargamel's size prevents him from using the portal himself, so he sends Vexy on the mission to kidnap Smurfette.
Witnessing Smurfette’s abduction, the Smurfs alert Papa, who conjures magical crystals for several of them to journey to their human allies, Patrick and Grace Winslow, in New York City. Initially, Papa intended for Brainy, Hefty, and Gutsy to travel, but an accident results in Clumsy, Grouchy, and Vanity using the crystals instead. They arrive at the Winslows' apartment just after celebrating their son Blue's fourth birthday, where they also encounter Patrick’s stepfather, Victor Doyle. Once informed of Gargamel's whereabouts in Paris, the group embarks on a mission to rescue Smurfette.
Upon reaching Paris, Patrick and Victor devise a plan to distract Gargamel during one of his performances at the Palais Garnier, while the Smurfs try to find Smurfette in Gargamel's dressing room. In an unexpected twist, Smurfette manages to escape her confines, leading to a chase with the Naughties, who try to convince her to join them by exploring a cheeky side of fun together.
As they return to Gargamel's hotel suite, he presents Smurfette with a tiny dragon wand as a deceptive gesture of goodwill. Yet, when Smurfette sees the Naughties suffering from a lack of essence, she reluctantly acquiesces to Gargamel's demands and writes down the Smurf creation formula. As a result, Gargamel transforms the Naughties into real Smurfs, only to ensnare them in his Smurfalator machine to extract their essence.
In a race against time, Patrick, Victor, and the Smurfs come together to rescue Smurfette. Sadly, the Smurfs fall into Gargamel’s trap and are captured, fueling Gargamel's large dragon wand. Just in the nick of time, Patrick and Victor manage to destroy the Smurfalator, creating an explosion of Smurf essence that dismantles the written formula and liberates the Smurfs. They all escape through a sewer hole and reunite with Grace and Blue. Although Gargamel attempts to regain control, he is defeated by Smurfette wielding her new wand, leading to his dramatic tumble onto the Notre Dame Cathedral and subsequent encounter with a living stone gargoyle.
In a heartwarming conclusion, the Smurfs bid farewell to the Winslows, returning home with Vexy and Hackus to enjoy a belated celebration of Smurfette's birthday.
In two post-credit scenes, Gargamel and Azrael find themselves pulled through the portal due to the aftermath of the Eiffel Tower fireworks, ultimately leading them back to their castle where a comical confrontation ensues.
