Eight years after the events of the first film, Sir Johnny English (Rowan Atkinson) is learning martial arts in Tibet as penance for an earlier failed mission in Mozambique. However, he is contacted by MI7, requesting he returns to service.
Johnny returns to MI7's London headquarters (now Toshiba British Intelligence) and assigned by new boss "Pegasus" (Gillian Anderson) to stop a plot to assassinate the Chinese Premier during scheduled talks with the Prime Minister. Johnny also meets with fellow agent Simon Ambrose (Dominic West) and MI7's resident inventor, Patch Quartermain (Tim McInnerny). He is also assigned a junior agent, Colin Tucker (Daniel Kaluuya).
In Hong Kong, English discovers an address that leads him to ex-CIA agent Titus Fisher (Richard Schiff). Fisher reveals that he is a member of a group of assassins called 'Vortex', who sabotaged English's mission in Mozambique. Vortex holds a secret weapon, which requires three metal keys to unlock, and Fisher reveals one. Fisher is killed by an assassin (Pik-Sen Lim) dressed as a cleaner, and the key falls into Vortex's hands. English is humiliated in front of the Foreign Secretary and Pegasus by the loss of the key, and assaults Pegasus's mother, mistaking her for the killer cleaner.
Kate Sumner (Rosamund Pike), MI7's behavioural psychologist, prompts English to recall the events of his mission in Mozambique, and the identity of the second Vortex operative, Karlenko (Mark Ivanir), a Russian spy. A golf match between Karlenko and English leads to multiple attempts on English's life. However, Karlenko is critically injured by the assassin, and English attempts to fly him to hospital. Before they arrive, Karlenko reveals that Vortex's last agent is a member of MI7, and dies.
In a meeting at MI7, it is revealed that talks between Britain and China will continue in a heavily guarded Swiss fortress called 'Le Bastion'. Over dinner, English informs Ambrose that he knows of a mole in MI7. Ambrose prepares to kill English, until it becomes clear that the traitor's identity is unknown. Tucker confronts Ambrose in the bathroom, knowing he is the mole, but English orders him to leave. Ambrose convinces English that Quartermain is the traitor. English entrusts the key to Ambrose, who tells Pegasus that English is the traitor.
English confronts Quartermain, and realises that he has been framed. He escapes in a modified wheelchair. English goes to Kate's house, and convinces her that he is not the traitor. Kate, scrutinising footage of the Mozambique mission, realises that the assassin behaved abnormally. They learn that Vortex owns a drug called timoxeline barbebutenol that allows them to control a person for a brief time before they die of heart failure. Ambrose, the only surviving member of Vortex, plans to use the drug to kill the Premier in exchange for 500 million USD.
English confronts Tucker and convinces him to help break into 'Le Bastion'. English warns Pegasus of the threat, and drinks the drug instead, rendering him vulnerable to Ambrose's commands. Ambrose orders English to kill the Premier using a pistol disguised as a tube of lipstick. English tries to resist the effects of the drug, and engages in a fight with himself while Tucker attempts to interrupt communication between Ambrose and English. Tucker disrupts the frequency, replacing it with radio station, resulting in English beginning to dance. Ambrose reasserts his command, revealing himself in the process. English resists, shooting at Ambrose, who escapes.
The effects of the drug wear off and English seemingly dies of heart-failure, before being revived by Kate, who kisses him on the lips, making his heart rate boost. English pursues Ambrose, parachuting from the building and hijacking a snow-mobile. English reaches Ambrose, who is in a gondola lift. The two fight, with English falling out of the car. Ambrose tries to shoot English, who shoots a rocket at the cable-car, killing Ambrose.
English is knighted by the killer cleaner disguised as the Queen. He chases and attacks her with a tray, before the cleaner is arrested and he realises he has mistakenly targeted the real Queen.
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