Sen was born into a Bengali family in Hyderabad. Her parents are Shuber Sen, a former Indian Air ForceWing Commander, and Subhra Sen, a jewelry designer and owner of a Dubai-based store. She has two siblings, a sister named Neelam and a brother named Rajeev.
Sushmita Sen made history by adopting a baby girl named Renée in 2000. She, as a single woman of only 25 years of age, was not viewed as socially acceptable to obtain the guardianship of the baby. However, the High Court of Bombay quashed the appeal and she obtained gain of cause. On 13 Jan, 2010 she adopted a three-month-old girl and named her Alisah.
At Miss Universe, Sen ranked third overall in the preliminaries, right behind preliminary winner Miss Colombia Carolina Gómez, and Miss Greece Rea Totounzi, who ranked second but won the preliminary swimsuit and evening gown competitions. Sen went on to place second, fifth and third in the swimsuit, India to the Miss Universe pageant from 2010 onwards through her project I Am She – Miss Universe India.
After her reign as Miss Universe, Sushmita became an actress. Her first film, Dastak was in 1996, in which she played the victim of a stalker played by Sharad Kapoor. Mukul Dev starred as the lead actor. She then starred in the 1997 Tamil, action film Ratchagan. Two years later her appearance as Rupali in David Dhawan's movie Biwi No.1 won her the Filmfare Best Supporting Actress Award in 1999. Biwi No.1 was the second highest grossing movie of 1999. The same year, she was also nominated for her role in Sirf Tum in the same category. Following her dance song in Fiza known as 'Mehboob Mere', she tried to make a niche for her career in the Indian film cinema.