Sen Sharma was born on 3 December 1979 Her father Mukul Sharma is a science writer and journalist and her mother Aparna Sen an actress and film director. She has an elder sister, Kamalini Chatterjee. Sen Sharma’s maternal grandfather, Chidananda Dasgupta, was a film critic, scholar, professor, writer and one of the co-founders of the Calcutta Film Society. Her grandmother Supriya Dasgupta was a cousin of legendary modern Bengali poet Jibanananda Das.

Sen Sharma made her debut as a child artist in the Bengali film Indira (1983). In 2000, she made her adult debut in the Bengali film Ek Je Aachhe Kanya, in which she played a negative character. It was followed by a role in Rituparno Ghosh’s acclaimed film Titli, opposite Mithun Chakraborty and her mother Aparna Sen.

Sen Sharma has a degree in English from St Stephen’s College, Delhi, which she received in 2001. She was a student of the Modern High School for Girls.

In 2001, she starred in the English-language film Mr. and Mrs. Iyer, directed by Aparna Sen. The film performed well mainly in multiplexes and was a major critical success. Sen Sharma’s performance as a Tamil housewife and her mastery of the accent were received well and she was awarded the National Film Award for Best Actress. Her performance was later included in the 2010 issue of the “Top 80 Iconic Performances” by Filmfare.

Sen Sharma was offered the lead role in Mira Nair’s Hollywood film, The Namesake (2007), but owing to clashing dates with other films, she could not commit to the project. However, she followed it with acclaimed performances as a mentally ill woman in 15 Park Avenue (2005) and as a middle age village woman in Omkara (2006). For the latter, she received both the Filmfare Best Supporting Actress Award and the National Film Award for Best Supporting Actress. Her next release Deadline: Sirf 24 Ghante (2006) got average reviews. In 2006, Sen Sharma made her directorial debut with an 18-minute Bengali short film titled Naamkoron (Naming Ceremony) for the Kala Ghoda Film Festival.

In late 2007, Sen Sharma acted in two movies under the Yash Raj Films banner. She noted her excitement toward these two projects as these were the first films in which she had to lip-sync for songs. In the first one, Laaga Chunari Mein Daag, a drama directed by Pradeep Sarkar, she portrayed the character of a Banaras small town young woman, Chutki, alongside Rani Mukerji. The film was a critical and commercial failure in India, even though her performance was received well. The second one was Aaja Nachle, which was widely promoted as the comeback film of Madhuri Dixit. The film did not do well. Rajeev Masand from CNN-IBN noted her performance in the film as being “…nothing short of fantastic. Her greatest strength is that she isn’t afraid of making a fool of herself and she doesn’t worry about being laughed at. As a result, her performance in Aaja Nachle is fearless and uninhibited.”

Sen Sharma started dating actor and co-star Ranvir Shorey in 2007. The couple got married on 3 September 2010 in a private ceremony. The Times of India reported that Sen Sharma gave birth to her first child, Haroon, on 15 March 2011 at a South Mumbai hospital. Sen Sharma and Shorey announced their separation in September 2015. They still remain friends and share the custody of their son. The couple finally got divorced on 13 August 2020.

In 2008, Sen Sharma starred in Dil Kabaddi. She starred in a short film (How Can It Be?) directed by Mira Nair for a movie project called 8, which was screened at several film festivals in 2008 before having a theatrical release.

In 2009, she appeared in the low-budget English-language film The President Is Coming, directed by Kunaal Roy Kapur, to generally positive reviews. Nikhat Kazmi from The Times of India wrote, “Performance-wise, it’s the uptight and complex-ridden Ms Konkona who walks away with laurels and laughs even as the film takes a healthy snigger at the desi self.”

In June 2009, Sen Sharma starred onstage first time at Atul Kumar’s The Blue Mug alongside Rajat Kapoor, Vinay Pathak, Ranvir Shorey and Sheeba Chadha. In 2010, the play was toured around the nation and abroad.

In 2010, Sen Sharma starred in Ashwani Dheer’s comedy Atithi Tum Kab Jaoge opposite Ajay Devgan and Paresh Rawal. and Neeraj Pathak’s Right Yaa Wrong where she played a lawyer. She has completed shooting for Rituparno Ghosh’s comedy film Sunglass and Vinay Shukla’s Mirch.

In 2011, Sen Sharma played the leading role in Aparna Sen’s Iti Mrinalini, reportedly a semi-autobiographical film directed by the acclaimed Indian director Aparna Sen, also Konkona’s mother. She will also appear in Amitabh Verma’s Jackpot opposite Ranvir Shorey, in Suman Mukherjee’s adaptation of Shesher Kobita and Goutam Ghose’s Shunyo Awnko.

In 2013, Sen Sharma starred in Balaji Telefilms’ Ek Thi Daayan, directed by newcomer Kannan Iyer and produced by Vishal Bhardwaj and Ekta Kapoor. The movie also stars Emraan Hashmi, Kalki Koechlin and Huma Qureshi, and the film itself is inspired by the short story written by her father Mukul Sharma. She has also played a lead role in Aparna Sen’s Goynar Baksho.

In 2015, Sharma starred in the Bengali film Kadombori as Tagore’s sister-in-law and also played Lakshmi Das, the wife of Gour Hari Das – an Odisha freedom fighter who spent 32 years attempting to convince the government of his patriotism. In October, she played a character based on Nupur Talwar in Vishal Bhardwaj’s film Talvar, regarding the 2008 Noida Double Murder case. The film premiered at the Toronto Film Festival to extensive critical acclaim for Sharma and her co-stars Irrfan Khan and Neeraj Kabi, and also became a sleeper hit in India. In the same year she played Nayantara in a short film, Nayantara’s Necklace.

In 2016, Sharma is working on A.R. Murgadoss’ film entitled Akira”, where she was portrayed a cop alongside Sonakshi Sinha.

In 2017 her directorial debut A Death in the Gunj released (2 June 2017), which starred Vikrant Massey and Kalki Koechlin in pivotal roles. The film was critically acclaimed and won her the best director award in the New York Indian film festival and also in the MAMI film festival. In July, her long-awaited Lipstick Under My Burkha released, directed by Alankrita Srivastava. The film garnered positive reviews and did well at the box office too. Her next project, titled Scholarship, alongside Kalki Koechlin is in pre-production.