MUMBAI SAGA is the story of a gangster and his rivalry with a cop. In the mid-80s, Amartya Rao (John Abraham) lives with his family, comprising of his father (Rajendra Gupta), brother Arjun (Harsh Sharma) and wife Seema (Kajal Aggarwal) in Mumbai. His family sells vegetables on the streets and are harrowed as they have to pay 'hafta' (bribe) to the goons of Gaitonde (Amole Gupte).
One day, Arjun argues with one of the goons who then throws Arjun off from a bridge. Amartya saves him in the nick of time before Arjun gets crushed under the train. Amartya till now had decided to not get involved with gangsters. However, he loves Arjun to death and the attack on him enrages him. He single handedly assaults Gaitonde's men and even chops off the hand of one of the goons. Gaitonde, who operates from the jail, tells the police to get Amartya arrested. Moreover, he puts Amartya in the same jail as him. Gaitonde's henchmen attack Amartya in the prison.
Yet again, Amartya single handedly defeats them. Gaitonde now realises that Amartya is too dangerous. The next day, Amartya is released on bail. This is made possible by Bhau (Mahesh Manjrekar), the unofficial king of Mumbai. Bhau offers Amartya to work for him and to find a solution to Gaitonde and his menace. In no time, Amartya learns the tricks of the trade. He also usurps Gaitonde's territory, between Dadar and Byculla. Gaitonde has no choice but to accept defeat. The story then moves 12 years ahead. Arjun (Prateik Babbar) has now grown up and Amartya sends him off to UK to protect him. Meanwhile, Sunil Khaitan (Samir Soni) is an industrialist who owns a mill, built by his ancestors. He wants to fire all the mill workers, demolish the mill and sell the land for an astronomical price. He takes the help of Gaitonde to evict the mill owners. Bhau tells Amartya to stop the Khaitaan Mill from materializing so that he can get the votes of mill workers. Amartya meets Sunil and warns him of dire consequences. Sunil complains to Gaitonde about Amartya's trend. In retaliation, Gaitonde tries to kill Arjun when the latter is in Mumbai on a short visit. Arjun escapes unhurt.
An angry Amartya then finishes off Sunil Khaitan in broad daylight. His widow, Sonali (Anjana Sukhani), goes to the police headquarters and announces that she'll reward Rs. 10 crore to the cop who kills Amartya. Vijay Savarkar (Emraan Hashmi) gets interested in this offer and decides that he'll kill Amartya, come what may. What happens next forms the rest of the film.