The film opens with a shot of the S.S. Libra cruising through the sea, when suddenly some helicopters appear overhead with Shadow Lugia, which picks up the ship. The sailors fall out and watch in awe as it flies away, carrying the ship with it.
The protagonist, Michael, finds himself using a Salamence to battle a Metagross. No matter what the outcome is, when the battle is over, Michael will then find himself in the Pokémon HQ Lab, where it is revealed that the battle was merely a simulation. Michael then speaks with Professor Krane and Lily. Prof. Krane comments on Michael's battle skills, and Lily remembers that she hasn't seen Jovi, Michael's younger sister, since lunch.
Lily asks Michael to look for her. Michael finds a P★DA that Professor Krane left him in his room and gets an E-mail telling him to ask Adon, who was playing hide-and-seek with Jovi. Adon tells Michael to look in Dr. Kaminko's house. After watching a report about the missing cargo ship that was carrying loads of Pokémon (the S.S. Libra), Michael goes to Kaminko's house, where he battles by Chobin, who mistakes him for a burglar. After fending him off, Jovi shows up and Michael takes Jovi home.
Back at the HQ Lab, Michael talks to Prof. Krane and obtains the Snag Machine, a machine that allows its owner to snag Shadow Pokémon from other Trainers. To complement the machine, Aidan adds a Shadow Monitor to the P★DA. When Professor Krane goes to ready the battle simulator for a test, some men come in and kidnap Professor Krane. Michael follows them outside and battles the leader, Naps, who is using a Shadow Teddiursa, which Michael snags. However, Prof. Krane is taken away by his captors. Aidan mentions that Prof. Krane is crucial to the Purification Chamber project (a device that allows Shadow Pokémon to be purified), and that there is nothing they can do without him. Lily then says they can complete it themselves, and sends Michael to Gateon Port to retrieve a crucial part, with Jovi tagging along.
At Gateon Port, Jovi runs into Zook, who sends out his shadow Zangoose in anger. Before he can do anything else, however, a mysterious wealthy man, Mr. Verich, steps in and has one of his bodyguards defeat Zook. Michael and Jovi retrieve the machine part from the mechanic Perr (snagging a few Shadow Pokémon on the way) and return to the HQ lab.
Lily mentions that there is a place in Agate Village that can purify Shadow Pokémon, and Michael heads there. While there, he meets Eagun, the elder of Agate Village, who shows Michael the Relic Stone, a stone that has the power to purify Shadow Pokémon. Eagun allows Michael to purify one Pokémon at the Stone, and Michael returns to the HQ Lab.
Michael then travels to the Cipher Lab to rescue Prof. Krane, and successfully does so while defeating Cipher Admin Lovrina. While at the lab, he finds a DATA Rom, and heads to Pyrite Town to speak with Secc and Nett at ONBS, to see if they can decode it. After receiving some tips from Duking about Pokespots, Michael receives a text from Nett saying to come back to Pyrite Town. Cipher has taken over ONBS, and it's up to Michael to defeat them on his way up to see Nett.
Michael's next stop is Phenac City. After his arrival, he finds that the city has been taken over by Cipher. After defeating the Cipher Peons, he heads into the Phenac Stadium and defeats Cipher Admin Snattle, freeing Phenac City.
Later, Michael is tipped off by Phenac's mayor about Cipher sticking around a strange building, and is also requested by a young girl in Pyrite Town to go save her Pokémon aboard the S.S. Libra; but both the strange building and the S.S. Libra are inaccessible due to the heavy sands that Michael's scooter can't pass. After another misunderstanding with Chobin, Michael is able to get advanced wheels that can take him through the heavy sands. Although Michael can find the specific creature he was requested to find, it flees when startled by the PDA, and all the other Pokémon supposedly aboard the ship have also disappeared. After encountering and dueling some more Cipher members, Team Snagem goons ambush Michael; by using Sleep Powder, they knock him out and steal his Snag Machine from him.
Michael then re-encounters Zook from Gateon Port at the Cipher Key Lair, the strange building Justy told him about, but he cannot even attempt to snag his Shadow Zangoose. Also, two bulky guards make the key lair inaccessible to Michael, leaving him trapped out.
Fortunately, Secc at ONBS directs Michael to Hordel at the Outskirt Stand; he directs Michael to the Snagem Hideout. After battling through the swarm of Snagem members, Michael defeats the leader Gonzap and reclaims his Snag Machine; but when they both realize that they are both trying to defeat Cipher, Gonzap agrees to help Michael through the guards. The same Gloom that put Michael to sleep puts the two bulky guards to sleep, letting Michael enter the Cipher Key Lair; after intensely battling through the many Shadow-enabled peons in it, and then after shutting down the factory thus ceasing the production of all Shadow Pokémon, Michael confronts and battles the third Cipher Admin—Gorigan.
After defeating the large, ape-like man, Mr Verich appears on video and reveals that he is actually Greevil, the true master of Cipher, and that he is hiding on Citadark Island, but the island is in a very stormy area of sea and almost always has terrible weather, making it almost impossible to breach. With the help of Makan, Michael—after getting the Master Ball from Professor Krane—enables the Robo Kyogre, and journeys to Cipher's last stronghold.
There, he battles through Lovrina, Snattle and Gorigan a second time and an entire horde of Pokémon, and even battles Ardos and Eldes, who are two more Cipher Admins and Greevil's bodyguards. After going through everyone, Michael battles Greevil after snagging or defeating Shadow Lugia. He defeats him, and it is then revealed that Ardos and Eldes are his sons. Ardos wishes to blow up Citadark Island, sacrificing Michael and all the Cipher members and Pokémon on the island so Cipher can live on, but he is ultimately spurned by Eldes, who convinces Greevil that Cipher is finished after being defeated a second time. Ardos storms off, and Eldes and Greevil decide to surrender to the police, thus ensuring Orre's safety.
Michael can complete the Orre Colosseum after this. The five Cipher Admins appear in competitions there, along with Gonzap and his Team Snagem followers as well as Chobin piloting Robo Groudon. Notably, when challenged Ardos hints of his plans to resurrect Cipher, and upon being defeated, he labels Michael as Cipher's biggest threat.
- Chandler Riggs as Michael
- Rowan Blanchard as Jovi
- Rachel Weisz as Lily
- Donnie Wahlberg as Professor Krane
- Richard Gere as Greevil
- Joaquin Phoenix as Ardos
- Casey Affleck as Eldes
- Peter Dinklage as Chobin
- Nicholas Hoult as Wakin
- Ryan Gosling as Zook
- Sean Penn as Dr. Kaminko
- Kay Panabaker as Lovrina
- Hugh Dancy as Snattle
- Lee Pace as Gorigan
- Trent Ford as Naps
- Sam Riley as Exol
- Daniel Radcliffe as Vander
- Arnold Schwarzengger as Duking
- Bobby Campo as Silva
- Josh Hutcherson as Nett
- Matthew Knight as Bitt
- Georgie Henley as Meg
- Ian McKellen as Eagun
- Mark Wahlberg as Miror B.
- Chris Hewsworth as Folly
- Liam Hemsworth as Trudly
- Sarah Silverman as Ancha
- Helen Mirren as Beluh
- Scott Speedman as Willie
- Rupert Grint as Justy
- Joel Courtney as Cail
- Rupert Friend as Perr
- Sam Rockwell as Makan
- Michael Keaton as Chief Sherles
- Patrick Dempsey as Officer Johnson
- Colin Ford as Secc
- Shantel VanSanten as Marcia
Chandler Riggs will wear a red wig for his role
Rowan Blanchard will wear a blue pigtail wig for her role
Kay Panabaker will wear a long pink pigtail wig for her role
It will distributed by Screen Pictures and Columbia Pictures with Pikachu the Movie