Emu, a clumsy pediatrics intern takes young Sota, who is suffering a mysterious illness, to the announcement event of the latest "Mighty Action X", Sota's favorite game. Emu became a medical doctor in order to save someone's life because his life had been saved once through surgery.

However, a mysterious virus emerges from Sota's body and the event turns into chaos. Emu hears from Asuna, an employee of the Ministry of Health, that transforming into a Kamen Rider can save the patient. Emu takes on this "operation" and inserts the Mighty Action X Gashat into the Gamer Driver, transforming into Kamen Rider Ex-Aid!

Becoming Kamen Rider Ex-Aid, Emu now must serve as both a pediatrician and a member of CR. A gifted surgeon named Hiiro Kagami comes back from the United States and is not only the son of the director, he’s also Kamen Rider Brave. This results in a clash of ethics when it comes to dealing with patients.

Emu follows a patient who’s fled in fear of a doctor and encounters Taiga, who transforms into Kamen Rider Snipe. Once Emu learns of the past connection Taiga had to CR, he visits the dark hospital Taiga resides in to rescue the patient.

Emu cannot transform into a Kamen Rider since Taiga stole his Gashat. Medical Examiner Kiriya Kujo appears before a crestfallen Emu. He brings a Bugster-infected patient and offers to steal back Emu's Gashat in exchange of helping Kujo out with his prodigious gaming abilities.

When the thief of the 4 new Rider Gashats is infected with the Bugster virus, Emu and Hiiro clash about saving his life or not, and the identity of the mysterious Kamen Rider that is attacking the others is finally revealed.

The girlfriend of the student that the Bugsters were after has contracted the Game Disease. Hiiro transforms into Brave and succeeds in separating the Bugster from the girl.

A hospitalized patient showing two symptoms of the Game Disease has appeared. Emu and Hiiro transform and succeed in separating the two Bugsters from the patient. But Genm appears again to interfere, letting the Bugsters escape.

Taiga manages to capture the Bugster which escaped in the last episode and obtains the Jet Combat Gashat, holding the Bugster, and thus the patient, hostage in exchange for the other Riders' Gashats. When they arrive to challenge him, he decides only he is needed to fight the Bugster, and tries to destroy Ex-Aid and Brave.

Graphite infects the Deputy Director-General of the Ministry of Health with the Bugster Virus, while the doctors at the CR fall out over the most important course of action: Save the Patient or defeat Graphite?

Unable to control the powers of the new "Drago Knight Hunter Z" Gashat only by himself, Emu discovers that to do so he must convince the other Kamen Riders into join forces with him. Once he tricks them into doing so, the time comes for their showdown with Graphite.

Emu gives Kiriya another chance to earn his trust. Kiriya then takes the chance to finally reveal Kuroto's intentions and expose him as the Black Kamen Rider that is working with the Bugsters.

With Christmas around the corner, Emu runs against time to defeat the Salty Bugster again and save another patient, while Kiriya's investigation leads him closer to the truth, but his life is in danger when he faces Kuroto's new power.

Apparently Hiiro wasn't the only accomplice that Masamune had in the palm of his hand! Cronus suddenly summons Kamen Rider Lazer Turbo Level 0 into the fight! In order to further expand the presence of Kamen Rider Chronicle around the world, Lazer Turbo stands before the Doctor Riders in an attempt to keep them from ending the game! Much to the shock of everyone, Kamen Rider Lazer Turbo finally reveals his identity...

Genm Corp. announces a new addition to Kamen Rider Chronicle, the "Cronus Capture Quest", and despite knowing what dangers lie ahead, countless new players join the game! Meanwhile, Emu is still reminded of the message Kiriya said to him before Masamune took him away. Kuroto completes an invincible golden Gashat holding an unbelievable amount of hidden power! Ex-Aid and the others rush to stop the "Cronus Capture Quest" as Brave and Lazer Turbo stand in their way once again...

Ex-Aid finally went Muteki and was able to beat Cronus! Masamune, who does not like the fact that Ex-Aid was able to attain a power that exceeded his control, angrily forces Hiiro to work for him as he claims Saki as a hostage! Brave forcibly renews his resolution, and this time he is able to transform into Legacy Gamer Level 100! Emu is more confused than ever, while Taiga is the only one who truly understands just how painful Hiiro's decision truly is…

Graphite mercilessly attacked the body of Taiga which forced him out of his transformation! The injured Taiga has been rushed to the hospital immediately, but there is a high possibility that his heart has been damaged. Moreover, it seems that it would take an expert-level of surgical expertise in order to save his life. After returning to Masamune, Hiiro's father and Asuna make an urgent phone call. The director asks Hiiro to perform Taiga's surgical operation. Just what decision will Hiiro come to in the end?

In order to deprive Ex-Aid of his transformation abilities, Cronus decides to target Parado directly. Para-DX without Emu is still not perfect, so he is beaten easily. Even so, Ex-Aid cannot stop chasing Cronus. However, Cronus was planning an underhanded scheme. Nico's game disease, which just started to show symptoms, belongs to that of Gamedeus, the Last Boss of Kamen Rider Chronicle! In order to defeat Gamedeus, Ex-Aid has to defeat both Graphite and Parado! Just then…Parado's hands begin to shake violently…

Parado has been defeated, and Emu has lost the ability to transform into Ex-Aid! Following Parado's annihilation, the other Riders team up in order to defeat Cronus. Brave, Snipe, Genm, and Lazer Turbo, all alternate the Hyper Muteki Gashat in order to counteract Cronus' Pause. Meanwhile, Emu was deep in thought. The fear of death that he felt at the moment of his extinction, even if he was a Bugster, he shared the same feeling as he did in that moment. Just then, Emu takes out the Mighty Brothers XX Gashat…

Kamen Rider Chronicle has been reset thanks to Masamune's special ability! Thanks to his Bugster infection, his hidden power has awakened, and the game is reset to the moment before Emu received the Hyper Muteki Gashat! Finally, with Parado having already been defeated, Graphite is the only game character left in order to clear Kamen Rider Chronicle! Brave and Snipe both challenge Graphite with a burning fighting spirit. Meanwhile, Emu believes that Graphite infected with Gamedeus' virus may be the only one strong enough to defeat Cronus. However, Graphite refuses to cooperate with the Riders…

The Last Boss of Kamen Rider Chronicle, Gamedeus, is finally born! If you defeat Gamedeus, then the game will end! However, at the moment of Gamedeus' revival, massive amounts of the Bugster Virus spread throughout the city! The number of infected patients are increasing, as well as the number of people being rushed to the hospital. While the doctors attend to the patients, Ex-Aid and Para-DX team up to fight Gamedeus! But their strength is far too weak against Gamedeus, as he sends them flying easily. At the same time, two people were confronting each other. Kiriya and Kuroto, both transformed, clash fists to see who's fate will be decided in the end…

Suddenly, the Gamedeus virus begins spreading through the streets! Masamune becomes Gamedeus Cronus and appears before the other Riders, as he summons Nico into the World of Kamen Rider Chronicle! Nico is the one who is qualified to challenge the Last Boss of Kamen Rider Chronicle as a Ride-Player, but it seems clear that Masamune is going to try to Game Over the player who is closest to beating the game in order to reset it. In an attempt to save her but unwilling to let the others follow, Taiga uses the Chronicle Gashats seized from patients and goes to find her. However, the other Riders cannot enter the World of Kamen Rider Chronicle! Just what will happen to Nico's fate?

Gamedeus Cronus has grown massive and become the strongest Last Boss! The Gamedeus Virus expanded and the pandemic has gotten worse. The Gamedeus Virus can now be transferred from person to person, turning the infected into Bugster Virus foot soldiers! Two Bugsters witnessing this symptom, Parado and Poppy Pipopapo, decide to take action. "There is something that only us Bugsters can do…" Poppy says as she rushes to Ex-Aid…

Though Gamedeus was finally destroyed at the cost of Poppy Pipopapo and Parado when they extracted the Bugster from his body, Masamune Dan survived and takes advantage of Emu no longer being able to use Hyper Muteki. The Kamen Riders are at a huge disadvantage, while Cronus doesn't hold back, and initiates Pause. All of the Kamen Riders' movements are frozen in time, and he prepares to kill them, starting with Emu…