A remote village named Pali in Andhra Pradesh is struck by an unknown disease, with several villagers dying each month. The village Tantric (Rao Ramesh) predicts that a powerful man will come to their rescue as God. He assigns his assistant Siddhappa (Shafi) the duty to find a man with such supernatural power, and bring him to their village.
Meanwhile, Alluri Seetarama Raju alias Raju (Mahesh Babu) is an eccentric Orange Cab driver who lives in Hyderabad, with his grandfather (Kota Srinivasa Rao), a teacher. Raju is currently in Rajasthan in search of the family of a man named Bilavar Singh. In his journey, He meets a Gemini TV television reporter Baabji (Sunil) who comes to Rajasthan to shoot a travel documentary.
Raju introduces himself to Baabji and tells him the reason for him being in Rajasthan. He describes a woman named Subhashini (Anushka Shetty), whom he considers brings bad luck to him. Previously he encountered her in various occasions in which she damages his taxi due to her reckless driving. Raju lands in hospital one day when Subhashini mixes epsom salt laxative intended for someone else, in Raju's coffee thinking that it meets her at a coffee shop to collect the compensation for his taxi's damages from her. For this reason, he considers her a bad luck.
One day, he drives two men, Geology Scientist Dr. Paranji and his assistant Bilavar Singh, to their destination the Geological Survey of India. But he sees them getting gunned down by some hench men and Bilavar falls out of a window and lands straight on Raju's taxi, completely destroying it. Since Bilavar has insurance, Raju's boss tells him to deliver the insurance check of Rs. 5,00,000 to Bilavar Singh's family in Girdwala, Rajasthan and get Rs. 1,00,000 in return to pay for his car damages.
Meanwhile, Subhashini's father, business magnate Durga Prasad (Tanikella Bharani), brings her a match, another business magnate GK's (Prakash Raj) son. The main reason for the proposal is to establish a strong business partnership. GK's son takes her to Rajasthan for a date. But Subhashini runs away after she sees a condom packet drop from his pocket and realizes his true intentions. GK finds out about it and informs Durga Prasad and promises to bring Subhashini back. He sends his henchman, Govardhan (Subbaraju) to Rajasthan in search of Subhashini. To Raju's dismay, Subhashini finds Raju and Baabji and learns that she is in Rajasthan. Subhashini, Baabji, Raju, and a botanist Tom (Ali) find Girdwala and hand over the check to Bilavar Singh's family, but Raju refuses to ask for the Rs. 1,00,000 when he sees the family's poverty. Tom remains in the village as the villagers want to punish him for cutting a sentimental plant, Baabji goes away with his shooting team, but does not offer them a ride as he is scared of Subhashini's reckless behavior.