After snatching his father Rohit Mehra's (Hrithik Roshan) life from the wicked Dr. Siddhant Arya (Naseeruddin Shah), Krishna Mehra (Hrithik Roshan in double role) lives a happy life with his father and wife Priya Mehra (Priyanka Chopra). Post conducting various scientific experiments, now Rohit aims to do a new one in which he can put life in a dead body with the help of sunrays. Rohit's son Krishna is unable to settle in one particular job owing to his tendency to help people in life-threatening situations, being blessed with superpowers. Krishna, who is Krrish, prefers to hide his real self from the world by leading a layman's life. Krishna's wife Priya is a television reporter with a leading news channel. Krishna and Priya are soon going to gift with a bundle of joy from the God.

There incepts an evil force on the other side of the world, who is called Kaal (Vivek Oberoi). He is the one, who possesses similar superpowers of that of Krrish, but utilizes in destroyal of human race for earning millions as per his business plan. Although Kaal is blessed with such powers, his body portion beneath his head is completely immobile and he can only move his two fingers, leaving him wheelchair-bound. For reaching his ultimate goal, Kaal creates a mutants gang, who are mixture of human beings and animals and thus, are named as 'Maanvars'. These evil looking maanvars operate on Kaal's finger tip. Kaal along with his team of scientists formulates a heinous virus that kills a human within seconds. His aim behind this, is to spread fear among the masses and to eat out a huge chunk of profit. This virus affects several lives in Namibia and eventually, Kaal plans to destroy Mumbai by spreading this lethal virus. The only medicine on this virus is the antidote made by Kaal's blood, which will help Kaal earn huge moolahs and be the superpower. According to his plan, Kaal commences his experiment in Mumbai, thereby killing many people with the virus. On knowing this, Krishna and his father Rohit attempts to save the city by inventing another antidote with their blood, after finding that the virus is ineffective on them, as they are superhumans. Kaal gets tremendously shocked after knowing another antidote other than his, is saving people's lives. This sparks the further combat between Krrish and Kaal, which is good versus evil