The central tragedy that propels the plot is the death of Sameer, Mandira's son. After 9/11, Sam faces bullying at his school due to his Muslim surname, Khan. His best friend, Reese, turns against him. During a fight on a soccer field, older bullies attack Sam, and he is fatally injured. Reese is present but is too afraid to intervene effectively. This devastating event is the direct result of the anti-Muslim hate that has permeated their community.
Consumed by grief, Mandira blames Rizwan, telling him that Sam died because of his name. In a fit of rage, she screams that to be with her again, he must go and tell the President of the United States that his name is Khan and he is not a terrorist. Rizwan, taking her words literally, embarks on his cross-country journey. Along the way, he is detained and interrogated as a suspected terrorist after being overheard praying at an event. He later becomes a hero in a small Georgia town named Wilhelmina by helping the predominantly African-American Christian community save themselves from a hurricane. This act of selfless heroism gains him national media attention, turning "My Name Is Khan" into a slogan for a movement of tolerance.
The climax occurs when Mandira, having seen Rizwan's journey on the news and filled with remorse, reunites with him. Just as they reunite, Rizwan is stabbed by a radicalized individual who views him as a traitor to Islam. He survives, and upon his recovery, he finally gets the chance to meet the newly-elected President Barack Obama. He delivers his message: "Your name is Khan and you are not a terrorist." The film ends with Rizwan and Mandira walking away together, their love reaffirmed and his promise fulfilled.