She won the Filmfare Award for Best Supporting Actress for her performance as the girlfriend of a married man in the comedy film Biwi No.1 (1999), and was also nominated in the category for her roles in the dramas Sirf Tum (1999) and Filhaal... (2002).

[4] After a career downturn and hiatus, Sen starred in the drama series Aarya (2020–2024), winning a Filmfare OTT Award, and portrayed transgender activist Shreegauri Sawant in the miniseries Taali (2023).

[6][7] She has a younger brother named Rajeev Sen, who was married to television actress Charu Asopa.

[8] Sen attended Air Force Golden Jubilee Institute in New Delhi,[9] and St. Ann's High School in Secunderabad.

She enrolled in a bachelor's degree in Political Science in the 2007–08 academic session at School of Open Learning, Delhi University but withdrew her admission later.

[17][18] In January 2016, Sen appeared as one of the judges of Miss Universe 2016 at the Mall of Asia Arena, Pasay, Metro Manila, Philippines.

[24] In 1999, Sen earned wider recognition with her portrayal of Rupali Walia in David Dhawan's comedy film Biwi No.1, alongside Salman Khan and Karisma Kapoor.

[26] The same year, she received a second nomination for the Filmfare Award for Best Supporting Actress for her performance as Aarti in the romantic drama Sirf Tum.

[29] In 2001, she first appeared opposite Govinda in the fantasy comedy Kyo Kii... Main Jhuth Nahin Bolta.

[32][33] Priya Ganapati of Rediff.com noted, "Sushmita Sen's role of Neha deserves an extra round of applause.

[38] Taran Adarsh of Bollywood Hungama noted, "Sushmita Sen, cast in a challenging role, does full justice to her part.

[40] Her career's biggest success came with the action masala film Main Hoon Na, in which she played the role of a chemistry teacher opposite Shah Rukh Khan.

[41][42] Taran Adarsh of Bollywood Hungama noted, "Sushmita Sen looks like a million bucks and her on-screen chemistry with SRK is fantastic.

She first portrayed a dutiful nurse in her third film with Salman Khan, the romantic comedy Maine Pyaar Kyun Kiya?.

[49] In 2007, she played a widow in the action drama film Ram Gopal Varma Ki Aag, opposite Prashant Raj Sachdev.

[51] In 2009, Sen first appeared in the critical failure drama film Karma Aur Holi opposite Randeep Hooda.

In 2015, she starred in a Bengali drama film titled Nirbaak, marking her comeback opposite Anjan Dutt.

"[59] Post a hiatus of five years, Sen made her web debut in 2020 with Disney+ Hotstar's crime thriller Aarya.

[5][66] Sen was diagnosed in 2014 with Addison's disease and was told she would require lifelong steroid drugs to manage the illness.

"I healed in time, my adrenal glands woke up, no more steroids, no withdrawals and no auto-immune condition as of 2019," Sen stated.