Rahul Mithaiwala (Shahrukh Khan) is a forty-year-old bachelor living in Mumbai. His parents died in a car accident when he was eight years old, so his grandparents raised him. His grandfather (Lekh Tandon) owns a chain of confectionery shops. Before his grandfather's 100th birthday celebrations, two of Rahul's friends invite him to accompany them on a vacation in Goa, which he accepts. Rahul's grandfather dies on the eve of the celebrations. His grandmother tells Rahul that his grandfather wanted his ashes to be divided into two parts—one of each to be immersed in the Ganges River and Rameswaram. She asks Rahul to go to Rameswaram and immerse them. He reluctantly accepts her request but is also eager to attend the Goa trip. Rahul and his friends plan to dump the ashes at Goa but his grandmother wants to see him off, forcing Rahul to travel by train. He books a single ticket on the Chennai Express and plans to meet his friends along the way. Rahul forgets to take the ashes; he returns to collect them but almost misses the train. While trying to leave the train, he notices a young woman running to board it. He helps her and four other people to board the moving train but the train leaves the station before he can get off.
Rahul tries to flirt with the woman, who starts communicating by singing parodies of Hindi film songs, and explains that the four men are trying to kidnap her. Rahul lends her his mobile phone so that she can contact her friends, but the men with her throw it from the train. Rahul is annoyed but says nothing because the men are carrying weapons. Rahul tells the ticket inspector about them, but they push the inspector into a river below the bridge. Panicked, Rahul learns that the men,who are her cousins are kidnapping her and that her name is Meenalochni "Meena" Azhagusundaram (Deepika Padukone). She is trying to flee from a forced marriage to Tangaballi (Nikitin Dheer). Her father Durgeshwara Azhagusundaram (Sathyaraj) is a powerful headman of the local mafia in Tamil Nadu.
Rahul (Shahrukh Khan) helps Meenamma (Deepika Padukone) board the train, a spoof of the famous train scene in Khan's 1995 film Dilwale Dulhania Le Jayenge[20]
Meena takes Rahul to her father and introduces him as her lover. Tangaballi challenges Rahul to a duel to which Rahul accepts without knowing partly aided by his lack of knowledge in Tamil. On the night of the duel, Rahul escapes with the help of a local policeman Shamsher (Mukesh Tiwari) but he ends up on a ship with Sri Lankan terrorists and smugglers. A gunfire battle ensues between police force and terrorists. When police officers investigate an arrested Rahul, he tells his story and ends up in Komban Kaum again. Surrounded by Azhagusundaram's sickle-wielding henchmen, Rahul pretends to take Meena hostage and escapes with her in her father's car, battling Azhagasundaram's men. When the car breaks down, Rahul and Meena quarrel and part ways. Rahul, not knowing which way to go, returns to Meena who takes him to the Vidhamba village where a wedding is taking place. Meena tells the villagers that they are a married couple who have eloped and need protection and rest.
The villagers grow fond of the couple and take care of them. Meena realises that she has fallen in love with Rahul. When Rahul plans to sneak away, she argues, not wanting to earn the villagers' distrust. Tangaballi catches Rahul trying to leave, but the villagers help them escape again. Meena persuades Rahul to immerse his grandfather's ashes and travels with him to Rameswaram, where they complete the rites. On their way back, Rahul realises that he has fallen in love with Meena, and does not tell her where they are going. He takes Meena back to her father and tries to make him understand and honour his daughter's wish. He also tells Meena that he loves her. Rahul tells Tangaballi and his goons that he is ready for the fight this time. A strong battle ensues, where Rahul is severely injured but emerges victorious. Meena's father and Tangaballi reform and accept that the heart of a common man like Rahul is bigger than their physical ability and political influence. Azhagusundaram allows Rahul to marry Meena. When all ends well, Rahul leaves a message that love knows no regional or language barriers and that with a strong heart, there is no limit to what a common man can achieve.