The movie opens to show a well built man called Sanjay who goes about beating up and killing people. It is then seen that Sanjay (Aamir Khan) has a medical condition called "short term memory loss'. He leads a documented existence, he carries labelled photographs of people he knows and things that he wants to remember, such as his address, his doctor etc. His house contains detailed maps of Mumbai and drawers with labels in which he keeps the things he needs.
Sanjay is looking for Ghajini. His body is tattoed with writings about his past and the love of his life Kalpana (Asin Thothumkal), such that he is able to remind himself again and again about the tragedy that took place in his past and his mission in life.
Sunita (Jiah Khan) is a medical student who gets interested in this case. She comes across Sanjay and then seeks him out as she is mesmerised with his case. She inadvertently gets involved in his mission.
What happened in his past to make Sanjay the way he is? Will Sanjay be able to find Ghajini?