Gupta was born to R.N. Gupta. She did her M.Phil. in Sanskrit, and is a 1980 alumnus of National School of Drama, New Delhi. Neena Gupta was in a short-lived relationship with Vivian Richards in the eighties – they have a daughter, Masaba Richards

Gupta has made appearances in several international films, such as Gandhi (1982), in which she played the niece of the Mahatma Gandhi, and the Merchant Ivory films The Deceivers (1988), In Custody (1993), and Cotton Mary (1999).

She starred along with Madhuri Dixit in Khalnayak (1993); she was featured in the popular song 'Choli ke peeche' in the movie. She has made the telefilms Lajwanti and Bazar Sitaram (1993), which won the 1993 National Film Award for Best First Non-Feature Film.

Her big break on television came with Khandaan (1985), Gulzar's Mirza Ghalib (1987), a TV miniseries, followed by Shyam Benegal's Bharat Ek Khoj (1988) and later Dard (1994 DD Metro), Gumraah (1995 DD Metro), Sans (Star Plus), Saat Phere (2005), Chitthi (2003), Meri Biwi Ka Jawab Nahin (2004), and Kitani Mohabbat Hai (2009) .

She also hosted the Indian version of the TV series The Weakest Link, Kamzor Kadii Kaun (Star Plus), and appeared in Jassi Jaissi Koi Nahin (Sony TV) which gave her considerable popularity.

She has also directed successful TV series, such as Saans (1999), Ans Siski in (2000) and Kyun Hota Hai Pyarrr. She currently plays the role of Shubha, one of the four women main leads in Ladies Special, a daily soap on Sony TV.

She also run a theater production company, 'Sahaj Productions' with actor, Rajendra Gupta, and acted and produced Hindi play Soorya Ki Antim Kiran Se Soorya Ki Paheli Kiran Tak.

She had a brief affair with former West Indian cricketer Vivian Richards, with whom she has a daughter, Masaba. She was also involved in relationships with Alok Nath and Sharang Dev. On 15 July 2008, she married New Delhi-based Vivek Mehra, a chartered accountant, in a secret marriage in the United States.

Rohini Hattangadi (1985) · Vijaya Mehta (1986) · Manjula Kanwar (1987) · Surekha Sikri (1988) · Uttara Baokar (1989) · Uttara Baokar (1990) · K.P.A.C. Lalitha (1991) · Santha Devi (1992) · Revathy (1993) · Neena Gupta (1994) · Surekha Sikri (1995) · Aranmula Ponnamma (1996) · Rajeshwari Sachdev (1997) · Karisma Kapoor (1998) · Suhasini Mulay (1999) · Sudeepa Chakravarthy and Sohini Haldar (2000)

K.P.A.C. Lalitha (2001) · Ananya Khare (2002) · Raakhee Gulzar (2003) · Sharmila Tagore (2004) · Sheela (2005) · Urvashi (2006) · Konkona Sen Sharma (2007) · Shefali Shah (2008) · Kangana Ranaut (2009) ·