The plot of the film revolves around bringing together the lives of several individuals beginning with the 12th century and ending with the 21st century; the main person being a research scientist who develops a bio-weapon and makes sure that it is not acquired by a group of terrorists. Several other people also get involved in the process and all their stories connect after the striking of a tsunami, thus bringing in philosophical views into the picture.
Govindarajan Ramaswamy (Haasan), a bio-scientist speaks from the Jawaharlal Nehru Stadium about the Chaos theory and the Butterfly effect. He begins by reciting events from the 12th century in Chidambaram, when king Kulothunga Chola II (Napoleon), a Saivite, persecutes Vaishnavites and intends to destroy an idol of Govindaraja. Rangarajan Nambi (Haasan), a Vaishnavite, protects it and offends the king. The king orders Rangarajan to be executed by being submerged into the sea with the idol.
On 20 December 2004, a bio-technology lab in the USA designs a virus (combination of Marburg and Ebola) intended as a bio-weapon. After understanding its potential, Dr. Govind (Haasan), one of the scientists involved, refuses to give the vial (containing the virus) away due to fear of misuse. However, his boss, Dr. Sethu, has other plans and tries to sell it to a terrorist group when Govind flees with it. Christian Fletcher (Haasan), an ex-CIA, follows him and attempts to seize the vial, when it is air couriered to India by accident. Govind sneaks into the aircraft carrying the virus and changes its location. After arriving in India, he is questioned by Balram Naidu (Haasan) (Pranab Kundu in Hindi version), a RAW operative. Govind unsuccessfully tries to explain the series of incidents.
In the meantime, Fletcher, who has married Jasmine (Mallika Sherawat), and arrived in India, using her as a translator, threatens Govind and takes him away in a jeep with a police officer. After exiting the city, Govind escapes from Fletcher and reaches Chidambaram. Fletcher follows him, after getting a cab, along with Jasmine. After Govind attempts to persuade the receivers of the package carrying the virus, it finds itself inside an idol of Govindaraja. In the chaos, Jasmine is killed.
Govind and Andal (Asin), who is the granddaughter of Krishnaveni (Haasan), an old woman for whom the package was sent, try to run away from Fletcher, and arrive in a ground where illegal sand miners are working. They try to rape Andal, but in the ensuing fight, Govind defeats the sand miners and they sneak out after the interference of Vincent Boovaragan (Haasan), a radical Christian, and save the family of Khalifulla (Haasan) from a car-crash in the process. One of them, a lady, faints suddenly and is taken to a hospital, where Govind procures a cooling box to store the weapon, as it is unstable and its temperature needs to be maintained. He meets Avatar Singh (Haasan), a pop singer, who is also there for treatment of his throat cancer. His prescription drugs are in a similar-looking box and before leaving the hospital, he unknowingly switches it with Govind's box.
Fletcher follows them and takes Andal and the Muslim family hostage in their house, from where Govind is blackmailed to bring back the box he is carrying. Unable to do anything, he reaches the place, only to find out that Avatar Singh must have the weapon. The police surround the house, forcing Fletcher, Govind and Andal to flee in a jeep. Shinghen Narahsi (Haasan), a Japanese martial arts expert, whose sister had been killed by Fletcher, follows them. Avatar Singh finishes his last performance and discovers the blunder, only to get shot by Fletcher after having a row. Govind and Andal flee to reach a construction site, where Govind takes out the weapon before giving the idol to Fletcher.
The sun dawns on 26 December 2004. Govind gets an idea from some drainage workers to immerse the virus in a large quantity of salt to destroy it. He goes to the sea, only to be stopped by Fletcher. Shinghen Narahasi arrives and fights with Fletcher. Both Narahasi and a motivated Govind fight Fletcher together and defeat him. Fletcherh opens and swallows the virus. Suddenly, a tsunami strikes, washing away Fletcher, and causing great destruction along the coast. Poovaragan's house is struck and he dies in a car after saving a child. Andal, Govind and Narahasi get into a boat. Krishnaveni arrives and begins to cry after perceiving Poovaragan as her long-lost son.
After relief measures are taken, Andal argues that god had sent forth the tsunami to get rid of the weapon. Govind responds by asking if god would destroy hundreds of lives to save millions.Then the shot zooms back where it is shown that they were talking in front of the idol submerged in the twelfth century. The scene shifts to the stadium, where Avatar Singh, who had his cancerous growth taken away by the shot he received, along with several others, listening to the speech by Govind, followed by former president George Bush (Haasan) as the credits roll.