During November 2007, San Francisco-based autistic Rizwan Khan, en-route to meet President George W. Bush so that he can convey that his name is Khan and he is not a terrorist, recalls his life, initially with his Bombay-based dad, Dilawar Amanaullah Khan; mom, Razia; and brother, Zakir. Dilawar works for the State Transport workshop in Borivali, and Rizwan accompanies him, learns the trade, and can repair virtually anything. After his passing, Rizwan is abused by his classmates, as well as by Zakir, who feels neglected, so she hires Wadia to teach Rizwan. Years later, Zakir decides to re-locate to U.S.A., and once there, gets married to Hasina. He sponsors Razia and Rizwan, but Razia passes away.
In San Francisco, where Zakri runs 'Mehnaz Herbal Beauty Products', Rizwan is hired as a door-to-door salesman, while Hasina concludes that he has Asperger's Syndrome. While selling products, he meets with and is attracted to a Hindu Salon worker, Mandira Rathod, a single mother of Sameer, whose husband abandoned her and re-located to Australia.
Both Rizwan and Mandira decide to get married much to Zakir's chagrin, who asks Rizwan to leave. The trio re-locate to Banville, open their own salon, encounter racial profiling after the 9-11 terrorist attacks, are blacklisted, shunned and suffer losses, and then Sameer gets killed. Mandira blames Rizwan for her plight and asks him to leave, while she decides to pursue Sameer's death with Detective Miguel Garcia.
Rizwan sets on his journey to meet Mr. Bush - little knowing that soon he will be detained as a terrorist suspect himself and held at an unknown location.
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