Born on November 19, 1975, in Hyderabad, India, Sushmita Sen hails from a Bengali Baidya family. Her father, Shubeer Sen, served as a Wing Commander in the Indian Air Force, and her mother, Subhra Sen, is a jewelry designer and owner of a Dubai-based store. She has a younger brother named Rajeev Sen.

Sushmita Sen's career took off when she won the Femina Miss India pageant at the age of 18, which led her to the Miss Universe 1994 contest. She emerged victorious, becoming the first Indian to win the Miss Universe title.

Sushmita Sen made her acting debut in 1996 with Mahesh Bhatt's thriller 'Dastak'. She then starred in the Tamil-language romantic action film 'Ratchagan' in 1997. In 1999, she won the Filmfare Award for Best Supporting Actress for her portrayal of a model in David Dhawan's comedy-drama 'Biwi No.1'. Her other commercially successful films include 'Aankhen' (2002), 'Main Hoon Na' (2004), and 'Maine Pyaar Kyun Kiya?' (2005).

After a career downturn and hiatus, Sushmita Sen returned to the screen with the drama series 'Aarya' (2020–2024), winning a Filmfare OTT Award. She also portrayed transgender activist Shreegauri Sawant in the miniseries 'Taali' (2023).

Sushmita Sen is known for her inspiring fitness journey. She often shares videos of her trying new things like aerial yoga and martial arts. Her diet includes vegetables, grilled fish, neem and honey concoction, warm water, fresh fruits, dal, cauliflower sabzi, chapatis, fish, and brown rice.

Sushmita Sen has been in relationships with notable figures such as actor Randeep Hooda, model Rohman Shawl, and businessman Lalit Modi. She dated Hooda from 2004 to 2006 and Shawl from 2018 to 2021. In July 2022, it was revealed that she was dating businessman and IPL founder Lalit Modi.

Sushmita Sen has received various awards for her performances. She won the Filmfare Award for Best Supporting Actress for 'Biwi No.1' in 1999. She also won a Filmfare OTT Award for her role in 'Aarya'. Additionally, she has received the Rajiv Gandhi Award, IIFA Award, 2 Filmfare Awards, 3 Star Screen Awards, and 3 Zee Cine Awards.