Two human children (played by Justin Bieber and Sara Gilbert in matching outfits), who are outcasts at their school because their parents are scientists, run away to escape the jeering cruelty of their peers. The children get lost in a dense wood where they are captured by bears. The bears leave the children in a mud-trap to forage for more human children. While the bears are away, a group of tiny blue (computer animated) creatures who call themselves Smurfs emerge from the foliage and set the children free. They take them back to their village and teach them of the Smurfing-Way. There (in an inspiring montage scene set to the pop song “Climb” by Miley Cyrus), the children learn about tolerance and acceptance. After a Smurfy Initiation Ceremony, they learn to sing the Smurfing-Song that will summon help from all the woodland creatures.
Whilst the children are there, the Smurf village is attacked by the evil wizard Gargamel (played by Colin Farrell) and his cantankerous and wise-cracking cat, Azrael (a computer animation voiced by Ellen Degeneres and pitch-shifted to a lower register). Gargamel is the sworn enemy of all Smurfs and has in the past sought to eat and/or use the Smurfs in Alchemy experiments. Now, however, Gargamel wants to use the Smurfs in powdered form to make weapons of mass destruction. In the chaos, Azrael manages to capture Poet and Jokey Smurf (both voiced by Rob Schneider).
The angered Smurfs, led by Hefty Smurf (voiced by Toby Keith), immediately set out to rescue the kidnapped Smurfs. Papa Smurf (voiced by Morgan Freeman) warns them not to be hot-headed, but to think and plan carefully. Some local woodland birds warn the Smurfs of Gargamel’s plans to create weapons of mass destruction and to sell the weapons to Mrs. Balthazar (played by Ian Mcshane). The children recognize the name and tell the Smurfs that Mrs. Balthazar is a rich and evil real estate developer who wants to level the public housing estate where the children live to erect the largest footwear outlet-mall in the Universe. The children join the fight and help the Smurfs prepare for battle by teaching them the ways of science. (Another climactic montage scene set to the song “Red Barchetta” by Rush.)
Late that night, disguised as pizza delivery men, the children knock on the door of Gargamel’s castle. Knowing that Azrael will answer the door and that he has an insatiable appetite for pizza, the children give him three boxes of pizza and many bottles of soda. They charge a nominal fee to avoid Azrael’s suspicion. Azrael immediately scarfs the pizza and sodas, but not before recognizing the children’s faces. Too late! The pizzas were made of solid baking soda and the bottles were filled with vinegar. Azrael begins to swell to gigantic proportions and spews tons of white foam that quickly floods the castle grounds. Gargamel, who is terrified of getting his clothes wet, is left to scream and cower in the highest tower, his once great mind addled by terror. The tiny army of Smurfs storms the castle and rescues the two captive Smurfs. On their way out, they deflate the miserable Azrael, who at last sees the evil of his gluttonous ways and says flatly, addressing the camera directly, “I guess ‘fat’ does rhyme with ‘cat’.”
After much rejoicing with the Smurfs, the children return to their own town with a little Smurf magic and a whole lot of confidence. When the school bully (featuring a cameo performance by Keith Richards) again attempts to administer his usual brand of playground abuse, calling the children “Bunsen burner victims” and “beaker babies”, the children summon the woodland creatures with the magic Smurf-song. The bully is dragged into the forest by muddy bears never to be seen again. The final scene is of a large dilapidated and almost illegible sign near the children’s housing estate that says “Future home of Mrs. B’s Nasty Shoe Palace”