Her actual film debut was in Ek Je Aachhe Kanya in 2000, before that she appeared only sporadically as a child actress. After appearing in a movie by Rituparno Ghosh, she became known to a wide audience for her role in Mr. and Mrs. Iyer (2002) under the direction of her mother. Sen Sharma plays a young Tamil woman who rescues a foreign Muslim from Hindu fanatics by spending him as her husband. Her acting performance earned her a National Film Award for Best Actress. The following films "Page 3" and "15 Park Avenue" won her critical acclaim again and prices. At 15 Park Avenue she plays a schizophrenic woman, the role of her caring sister took over Shabana Azmi. Her final breakthrough, also in German-speaking countries, came in 2007 with a starring role in Laaga Chunari Mein Daag - The Way of a Woman by Rani Mukerji, as well as Abhishek Bachchan, Jaya Bachchan and Anupam Kher.
In early 2007 Konkona Sen Sharma was awarded a Filmfare Award for her supporting role in Omkara (2006). Her most recent role was in Traffic Signal (2007). Since September 3, 2010 she is married to her co-star Ranvir Shorey. On March 15, 2011, she gave birth to a son in South Mumbai Hospital.