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, making her an obvious choice for winner. Following her famous dance item song in Fiza known as 'Mehboob Mere', she tried to make a niche for her career in the Indian film cinema.
Sushmita plays the role of a successful supermodel called Shimmer in Dulha Mil Gaya, the film was a major commercial failure that year.
Sushmita has signed three big projects, one of which reportedly has her portraying the slain Pakistan Peoples Party leader Benazir Bhutto in a film co-produced by Zaid Aziz and Henna Rai of the Karachi production company Vox Vision, and Leicester-based Sum Films. Tentatively titled Benazir Bhutto: The Movie, the film will be shot in locations in Pakistan, the US, Britain and Dubai, where Bhutto spent years as a student and later as a political leader in exile. When Sushmita was asked about this big opportunity, she excitedly said, “Yes, I am keen to play the role.”The second is Farah Khan's untitled venture opposite Salman Khan, with the third one being veteran actress Rekhha's biopic titled "Sitare" under the banner of Red Chillies Entertainment.