Mira Nair initially wanted Rani Mukherjee to play the role of Ashima after she had seen her in Mani Ratnam's Yuva. Rani Mukherjee couldn't sign the film due to date problems. After that, Mira Nair wanted Konkona Sen Sharma to play the role. She couldn't commit due to her mother Aparna Sen's film 15 Park Avenue. After which the director signed Tabu for the role.
Many of the "New York" interiors, such as the disco, Moushimi's apartment, the honeymoon suite, etc., were actually filmed in Calcutta to save costs.
Mira Nair originally wanted Abhishek Bachchan to play the part of Gogol, but changed her mind as she wanted someone who looks like he is raised in the US, so she cast Kal Penn as he was very keen to do the role, and also because Mira Nair's son wanted Kal Penn to do the role.
According to Kal Penn during an interview on The Late, Late Show with Craig Ferguson, Mira Nair's son and his good friend, who are fans of Harold and Kumar Go to White Castle, were adamant that she cast him as Gogol.
Tabu admitted that in all the years she had lived in India, she had never seen the Taj Mahal. The scene in the movie where the family goes to see the Taj Mahal was her first time seeing famous tomb.
In the ending credits of the movie Kal Penn is listed twice. He is credited as Kal Penn playing Gogol and Kalpen Modi playing Nikhil.
The novel's author (Jhumpa Lahiri) and much of her extended family were used in party/funeral scenes for the family in the U.S. because Mira Nair stayed at Lahiri's home and met much of her family. She thought they had a look she was trying to achieve, and that they were lovely people.
Jhumpa Lahiri, whose book the film is based on makes an appearance in the movie as "Jhumpa Maushi".