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Eight years after the events of the first film, former Sir Johnny English (Rowan Atkinson) is learning martial arts in Tibet as penance for a botched mission in Mozambique which resulted in him being stripped of his Knighthood. However, he is contacted by MI7, who arrange for him to be flown back to London and call him back 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 quartermaster, 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 'Vortex', a group of three assassins and several accomplices, who sabotaged English's mission in Mozambique. Vortex holds a secret weapon, which requires three metal keys to unlock when used together, and Fisher reveals that he is in possession of one. Fisher is then killed by an assassin (Pik-Sen Lim) disguised as a cleaner and the key falls into the hands of a Vortex member.
English chases the Vortex agent across Hong Kong and eventually retrieves the key from him. On a flight back to London, Johnny gives a suitcase containing the key to a flight attendant, who is revealed to be another Vortex agent. 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 behavioral psychologist, uses hypnosis on English to help him recall the events of his mission in Mozambique, and the identity of the second Vortex operative, Artem Karlenko (Mark Ivanir), a Russian spy. Johnny meets him at an exclusive golf course outside London. As they are playing golf, the same assassin from Hong Kong reappears and uses a sniper rifle disguised as a golf club to attack the party, claiming the life of Karlenko's bodyguard and critically injuring Karlenko. Johnny takes Karlenko and escapes the golf course in a helicopter. They fly to the nearest hospital, and before dying, Karlenko reveals that the third assassin in Vortex is a member of MI7.
In a meeting at MI7 with Pegasus and the British Prime Minister, it is revealed that talks between Britain and China will continue in a heavily guarded fortress called 'Le Bastion' in the Swiss Alps. 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 scolds Tucker and orders him to leave. Ambrose convinces English that Quartermain is the traitor. English entrusts the key to Ambrose, who then tells Pegasus that English is the traitor.
English confronts Quartermain in the church and realizes that he has been framed. He is then shot at by MI7 snipers and agents posing as worshippers in a church, using suppressors on their guns to fool the priest. He is shot once in the left leg and fools Quartermain before escaping in a modified electric wheelchair after holding Quartermain at gunpoint. English goes to Kate's flat, and convinces her that he is not the traitor.
Kate, scrutinizing footage of the Mozambique mission, realizes that the assassin behaved abnormally. They learn that Vortex owns a lethal drug called timoxeline barbebutenol that allows them to control a person for a brief time before that person dies 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 visits Tucker and convinces him to help infiltrate 'Le Bastion'. After passing through security at the fortress, English warns Pegasus (who now knows who the real traitor is) of the threat, and unknowingly drinks the spiked drink, 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 a song being played on a radio station, resulting in English beginning to dance. Ambrose reasserts his command, exposing 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. The paramedics try to save English with CPR but fail; he is eventually revived by Kate via a kiss on the lips, reviving him and making his heart rate boost. English pursues Ambrose, parachuting from the building and hijacking a snowmobile. English reaches Ambrose, who is in a cable car. The two fight, with English falling out of the car. Ambrose tries to shoot English, who shoots a rocket disguised as an umbrella at the cable-car, killing Ambrose. English then sits back and says happily â "Tucker, you clever boy!"
Because of his actions, English is due to have his knighthood reinstated by The Queen, but as the ceremony takes place, the apparent Queen reveals herself to be the killer cleaner dressed up as the Queen and attempts to kill English with the knighthood sword. English fends off the cleaner, to which she runs off. English attempts to catch and attack her, but when guards come in with the real killer cleaner. English realizes that he has assaulted the real Queen and has been tricked once again.
A post-credits scene, influenced by the barber scene in The Great Dictator, sees English preparing a meal for Kate to the tune of "In the Hall of the Mountain King".
Who informs Ambrose that he knows of a mole in MI7?
English