The movie revolves around Dr. Ajay “AJ” Kumar (Siddharth) who comes to Chennai (Hydrabad in the Telugu version) and introduces himself as Mano. He rents a house owned by elderly couple S.V.S Murthy (T. S. B. K. Moulee) and Jayam (Geetha). A do-gooder, Ajay lives life with a purpose. He gets along with everyone and wins the hearts of those whom he is close with. D. “Vidya” Vidyalakshmi (Nithya Menen), a newspaper photo journalist gets acquainted with him. Ajay is the sort of person who finds satisfaction in helping others. He sponsors the education of street children with the help of Vidhya who is attracted by his good nature. Things take a turn when she tells him about her feelings. Ajay, without informing her, decides to leave the city.
Meanwhile, flashback reveals that Ajay was a doctor in San Francisco where he meets Renuka “Renu” Narayanan (Priya Anand), an interior designer. They get married only to be told months later, that Ajay has Pancreatic cancer and he has about six months left – hence the title 180 (180 days). As Ajay is about to leave Chennai, Vidya meets with an accident and has to be operated upon immediately. Ajay takes Vidya to San Francisco for treatment. While in the San Francisco,he meets his friend,RJ “Sam” Sambasivam (Sricharan) who asks him to meet Renu, but Ajay leaves as he sees her life happier without him. It is revealed that earlier Ajay had faked his death to make Renu believe that he had died so that she would not suffer thinking about him every day. Now seeing her content, he decides not to meet Renu. He misses his flight to India and goes to Brazil instead. Now in Rio de Janeiro, he goes by the name Jose. He is seen playing football waiting for his death.