Mukherjee was born and brought up in Kolkata, India. Her father is a Marine Engineer and her mother is a jewellery designer. Besides theater, she developed a love for reading spiritual works, painting and writing poetry. She also underwent several years of training in the Indian classical dance form of Bharatanatyam. After graduating with a degree in English literature from Loreto College in Kolkata, she took up a hotel management course in New Delhi, but left it midway.
Mukherjee made her film debut in Phir Milenge, directed by Revathy. Around the time Phir Milenge happened to Mukherjee, Sekhar Kammula, a relatively new director from the Telugu film industry was in the process of casting for his next Telugu film, Anand, the film won 6 prestigious 2004 Nandi Awards bestowed by the Government of Andhra Pradesh. Her next film was Meenakshi in 2005, the film not finding much commercial success. In 2006, she appeared in two Telugu language films - Styleand Godavari and a Tamil language film, Vettaiyaadu Vilaiyaadu. Style was a dance-based film with actor-choreographers Prabhu Deva and Raghava Lawrence, Charmee Kaur and Raja, besides Mukherjee. Godavari was Sekhar Kammula's next film, starred Sumanth and Mukherjee in the lead roles. The film received predominantly positive reviews, and Mukherjee's role was particularly praised. She made her Tamil debut in 2006 in Gowtham Menon's Vettiyadu Velliyadu starring Kamal Hassan in which her brief role had an enduring impact. The film widely praised by critics and audiences alike and subsequently remade in Tamil and Kannada. In 2009, she played the role in Kutty Srank, directed by award-winning director, Shaji N. Karun and starring Malayalam matinee idol, Mammooty. The film swept the national awards, winning in six categories including Best Film. Kamalinee the opportunity to debut in her native language Bengali, in National Award winning director, Aniruddha Roy Chowdhary's Aparajita Tumi starring Bengali superstar Prosenjit Chatterjee. The film met with critical and commercial success and she garnered positive reviews. She performed in many theater plays and also modeled in advertisements for brands such as Neelkamal Furniture, Parachute, Fair & Lovely and Ayush. Her forthcoming movies are Iraivi, Puli Murugan.