Karthik is a Mechanical Engineering graduate in Chennai with poor results who aspires to become a filmmaker instead of an engineer. His friend introduces him to cinematographer Ganesh. With Ganesh's help Karthik becomes an assistant to director. Karthik's family, who are Tamil Hindus, rent Jessie's house. Jessie is from a conservative Malayali Nasrani Christian/Syrian Catholic family from Alappuzha, that lives upstairs.[8]

Karthik falls in love with Jessie the moment he meets her under her house, He tries to interact with Jessie, who is afraid of speaking to men around her strict father, and ends up angering her. Unable to hide his feelings any longer, Karthik confesses his love for her but she does not accept. A few days later, Karthik learns from his sister that Jessie has gone to Kerala to visit her grandmother. He and Ganesh end up in Kerala to look for her. After several days, he finds her and apologises. She introduces him to her family in Kerala as her "classmate". Jessie denies she has any feelings for him but agrees to only be his friend. However, on the train journey back home, Karthik purposely sits closely next to her and kisses her a few times but she eventually gently slaps him to make him stop. Karthik is convinced Jessie loves him and repeatedly expresses his love towards her and she continues to reject him by stating that her parents would not allow as both of them are from different religion and ethnic backgrounds as well she is a year older than him. The two meet several times and Jessie begins to realise that she also likes Karthik, but wants to refrain from any problems because she knows her father wouldn't accept the union. Consequently, due to various misunderstandings between Jessie's brother and Karthik, her parents learn of their supposed affair. They fix a match and scheduled her wedding. The day arrives and midway through the ceremony, Jessie refuses to marry the groom, displeasing everyone in her family. Karthik, who had, without anyone's knowledge, come to Kerala to witness the wedding is ecstatic and secretly visits Jessie at her home. It is then that Jessie admits she has indeed fallen in love with him. Karthik and Jessie continue to love each other without the knowledge of their parents.

At this point of time, Karthik goes to Goa on a 45-day shoot, where he gets rather busy. Meanwhile, the topic of Jessie's marriage comes up again at her home when the guy whom she refused to marry earlier pays them a visit. Panicking, Jessie calls Karthik and tells him that she wants to elope with him. Karthik, since he is traveling through less than ideal places, tells Jessie to stay in Chennai for now, and that soon he would be back and they can discuss. Jessie stops taking Karthik's calls and so he goes back one night to check on Jessie. He learns that Jessie has decided to break up, as the relationship is not peaceful due to her parents' disapproval. She says she has agreed to marry a boy of their choice. When Karthik pleads her not to do it, she tells him that a time had come when she was willing to elope, but the moment was gone. She doesn't want Karthik to wait for her too long, as he has his dreams to fulfill. Karthik later learns that she is married and has settled in the UK.

Two years later, Karthik meets Nandini. She falls in love with him, but is rejected by Karthik by saying that he hasn't yet gotten over Jessie. He then comes up with a script for his first film, which happens to be his very own love story and is shot in Tamil. He calls upon Naga Chaitanya as the film's protagonist, Samantha as the female lead and Ganesh as the film's cinematographer, and the film is eventually titled Jessie. While shooting for the film in New York, he sees Jessie and she comes to speak with him. Out of her anger, his parents leave in New York. She admits that she is not married and is still in love with him, and he too says she is still in his heart. Karthik and Jessie see around New York City. Karthik proposes yet again and they get married the same day. This is actually revealed to be the end scene in Karthik's film – which Karthik and Jessie in real life are watching together in the theatre. After it gets over, it is revealed to the audience that Jessie had in fact seen Karthik in New York but had not come forward to meet him. She is married now and hence asks Karthik to move on. She tells Karthik that they cannot lead a life which is full of obstacles as well as without parents approval and hence they depart separately, to lead different lives and different destinies.