Plot
In New York City, 12-year-old Emily Elizabeth Howard lives with her mother Maggie and has only one friend, schoolmate Owen Yu. Maggie leaves Emily in the care of her uncle Casey before going to Chicago for a business trip.
Mr. Bridwell, who runs an animal rescue tent at a park, introduces Emily to a small red puppy whose family had been taken by dogcatchers. He says that the puppy will grow based on how much love he receives. Casey rejects the adoption due to dogs not being allowed in the apartment building. When Emily gets home from school, she finds the puppy in her backpack and names him Clifford. Casey allows her to keep Clifford only for one night.
The next morning, Clifford has grown to giant proportions. Clifford eventually chases and plays with a man in an inflatable bubble in a park. Word of his existence spreads online. After learning from a vet's secretary of Bridwell's past miracles with animals and their owners, the Howards plan to get information on his whereabouts. Clifford eventually escapes from Casey's truck and humiliates Emily's bully Florence by licking her, which soaks her, giving Emily the friends she always wanted.
Zac Tieran, the owner of biotechnology company Lyfegro, learns of Clifford from his assistant Colette. Wanting to discover the secret of the dog's stature, Tieran contacts the police, falsely claiming to have genetically engineered Clifford, and leads a citywide manhunt for him. Emily and Casey are evicted from their apartment by superintendent Mr. Packard, who Tieran also tipped off, and pursued by the cops and Lyfegro after Emily refuses his bribe. Owen and Emily escape with Clifford in Casey's van, while their neighbors fend off Tieran's bodyguards. The three shelter in Owen's lavish pied-à-terre apartment, where Casey says that Clifford can stay with Emily provided that they find Bridwell and have him shrink the dog down to his original size. If Bridwell cannot be found, Clifford must be sent away to Shanghai, where Owen's father, Mr. Yu, owns an animal sanctuary. They race to the hospital, only to find a patient who says that Bridwell has died. Out of options, the two contact Mr. Yu, who arranges for a tugboat to take Clifford to a freighter to China. After Emily bids her companion a tearful goodbye, the tugboat sails away under the cover of night.
Law enforcement however intercepts the freighter due to Tieran's claim that Clifford was stolen; Clifford is airlifted via helicopter to Lyfegro. Casey soon learns that the person who died at the hospital was a different man, meaning Bridwell is still alive, so he and Emily try to save Clifford from being experimented on at Lyfegro, once again aided by friends from their neighborhood. They break into Lyfegro's headquarters and rescue Clifford, who flees through the city with Emily riding on him.
At Manhattan Bridge Park, Emily reunites with Bridwell. He says that he cannot make Clifford small again as it was her love that made him big. Bridwell advises Emily to advocate for Clifford and herself, and that being different is a gift. Emily explains to everyone the importance of love, regardless of differences. Tieran then arrives and says that Clifford's owner can be determined by scanning an ID chip his scientists secretly implanted earlier. Bridwell makes the chip identify Emily as Clifford's rightful owner, leaving Tieran to be fined for lying to the police and wasting police resources. Emily and Casey reunite with Maggie. As Owen prepares to take a group photo of Clifford, Emily, Casey, Maggie, and the neighbors, Clifford spots two people in inflatable bubbles in the park and chases after them while Casey rides in horror atop Clifford's back.
Packard later reverses Emily and Maggie's eviction by making Clifford his new assistant in the apartment building. Casey leaves his van and goes to work for Scholastic Corporation. He, Emily, and Packard paint a mural of Clifford, which resembles his hand-drawn counterpart, implying that Casey's new job is authoring and illustrating fictional books about Clifford. New York City residents band together to build Clifford a giant doghouse between the Jarvis & Jarvis law firm and Alonso's bodega.
