A year has passed since Eggsy Unwin and the secret organisation Kingsman saved the world from Richmond Valentine's neurological wave broadcast. He has since taken his late mentor Harry Hart's title of Galahad and lives with Crown Princess Tilde of Sweden. On his way home from the tailor shop, he is ambushed by Charlie Hesketh, a former Kingsman trainee who lost his arm and vocal cords during the Valentine incident. Eggsy evades Charlie with his henchmen in a car chase across London, but Charlie's severed cybernetic arm hacks into the Kingsman servers through the car's computer system. While Eggsy is away in Sweden, a volley of missiles destroy the Kingsman headquarters and wipe out all of the agents in Britain, including Eggsy's best friend Roxy. Brandon, a non-Kingsman friend of Eggsy's, is also killed in the attack.

Being the only surviving agents, Eggsy and Merlin follow the Doomsday protocol, which leads them to Statesman, a secret American organisation posing as a Bourbon whiskey distillery in Kentucky. There, they discover that Harry survived Valentine's gunshot a year earlier, but is suffering from amnesia. Eggsy and Merlin are briefed by Statesman head Champagne about a secret terrorist organisation called The Golden Circle. They begin their mission by following Charlie's ex-girlfriend Clara Von Gluckfberg. When Statesman agent Tequila develops a blue rash, he is replaced by agent Whiskey as Eggsy's partner. Eggsy manages to plant a tracking device on Clara during an encounter, but his revelation of the mission to Princess Tilde strains their relationship. After several failed attempts to cure Harry's amnesia, Eggsy triggers Harry's memories by threatening to shoot a Cairn Terrier that resembles Harry's late dog.

Poppy Adams, head of the world's largest drug cartel, broadcasts a message telling the world about a toxin she laced within every recreational drug available, which causes users to develop blue rashes before progressing through mania, paralysis, and ultimately, death. She also demonstrates the antidote on a captive Elton John and offers it to the world if the President of the United States ends his country's War on drugs and offers her organisation immunity. The President decides to have every affected user quarantined, including his Chief of Staff, Fox, with the intention of letting them all die and therefore ending Poppy's career. Eggsy, Harry, and Whiskey head to the antidote factory in Italy after intercepting a phone call to Charlie by Clara. Eggsy manages to steal an antidote sample, but it is broken by Whiskey during an ambush by The Golden Circle's henchmen. During the gunfight, Harry shoots Whiskey in the head, as he suspects that Whiskey is playing both sides, but Eggsy saves him with the same alpha-gel that Statesman had used to save Harry. Princess Tilde calls Eggsy in a state of mania, revealing that she has been affected by the blue rash. Eggsy, Harry, and Merlin discover the location of Poppy's hideout, "Poppy Land", in Cambodia and fly there to steal the remote control which deploys the antidote drones.

Upon their arrival at Poppy Land, Eggsy steps on a land mine, but is saved by Merlin, who sacrifices himself while taking the lair's guards with him. Eggsy and Harry storm through the lair and Eggsy kills Charlie while Harry destroys Poppy's robotic attack dogs with the help of Elton. They secure the briefcase with the access code to the drones and inject Poppy with a more potent dose of her toxin. She gives them the password before succumbing to an overdose. Before they can activate the drones they are stopped by Whiskey, who, having previously lost his pregnant wife to a crossfire from two methamphetamine users, is revealed to be working alone to ensure that all drug users are eliminated. Eggsy and Harry battle and brutally kill Whiskey in a fight. They release the antidote drones, saving millions of lives around the world.

In the aftermath, Chief of Staff Fox has the President impeached for conspiring to commit genocide on the drug victims. Champ announces that Statesman has acquired a distillery in Scotland to help rebuild Kingsman. To avoid the confusion of two Kingsman agents using the codename "Galahad", Champagne offers either Eggsy or Harry the agent title of Whiskey, but they decline. Instead, Statesman tech support agent Ginger Ale steps in to take the role. Eggsy marries Princess Tilde, and Tequila moves to London to work for Kingsman.

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