In 1988, she achieved national recognition for her role in the Hindi TV series Ganadevta and shot to wider fame and popularity after she played Draupadi in B. R. Chopra's Mahabharat (1988–90).

Popular Bengali TV series, she acted in, include Janmabhoomi (1997), Draupadi (2000), Ingeet (2001), Tithir Atithi to name a few.

[22] She achieved critical acclaim for her performance in National Award winning Bengali films such as Padma Nadir Majhi (1992) by Goutam Ghose,[23][24][25] Janani (1993) by Sanat Dasgupta[26][27] and Yugant (1995) by Aparna Sen.[28] She received BFJA Award for Best Supporting Actress twice for her roles in Amal Ray Ghatak's Ujan (1995) and Rituparno Ghosh's Antarmahal (2005).

[29] In the same year, she acted in the role of a conceited actress in Anjan Dutt's Tarpor Bhalobasa, which once again earned her critical acclaim.

[44][45] Ganguly was enjoined by Ramaprasad Banik to appear for a look test for the female lead in his Bengali TV series Muktabandha (1986).

[51] Roy's next venture was Agnitrishna (1989) that once again saw Chiranjeet Chakraborty essaying the male protagonist Abhijit suffering from pyrophobia.

[65] Onwards, she appeared in films such as K. Bapayya's Pyar Ka Devta (1991), Raj Sippy's Saugandh (1991) and Rajkumar Kohli's Virodhi (1992) to name a few.

In 1992, she acted in A. V. Seshagiri Rao's Telugu film Inspector Bhavani, where she played the character of a sincere police officer whose object is to bring an end to those who assassinated her fiancée.

[66] In the same year, she acted in Sukanta Roy's Bengali film Pitrireen, where she played the character of Sathi, a photographer who inquires about her father's assassin.

In 1992, she appeared in Goutam Ghose's award-winning Bengali film Padma Nadir Majhi, where she played the character of Kapila, a woman from the fishermen community who falls for her sister's husband and finally leaves her family to settle with him on Moynadeep island.

Utpal Dutt, who was also a part of this venture, was recorded to comment on her performance: "Roopa has really lived the life of Kapila with those flawless body languages of a woman from the fisherman community.

[68] In 1995, she appeared in Amal Roy Ghatak's Bengali film Ujan, which won her the BFJA Award for Best Supporting Actress in 1996.

[69] Apart from acting in feature films, she went on appearing in numerous telefilms and television series, both in Bengali and Hindi, including Sukanya (1998).

Though she made a cameo appearance in it, she garnered huge mass attention as the film was widely advertised on her enthralling dialogue; "Sagar dekhben naa, shudhu amake dekhun."

[71] In 2003, she appeared in Gautam Ghose's Bengali film Abar Aranye, where she played the character of Shimul, a buoyant woman who is grief-stricken at the deepest core of her heart for the probable loss of her husband.

[72] In 2005, she appeared in Rituparno Ghosh's award-winning Bengali film Antarmahal, where she played the character of Mahamaya, a docile wife to an arrogant zamindar.

"[76] Roopa Ganguly's Mahamaya is a worthy contender to lead any listing of memorable women characters from Ghosh's abundant array of some seriously multi-dimensional female protagonists seen on celluloid in recent times.

The film's narrator may be the British artist, but hers is the character that drives its most dramatic moments and through whom the audience is warned about the catastrophe in waiting.

From a jealous, wasted aging wife in the beginning, she seizes screen presence with her every appearance, lacing it with new untapped facets to her personality.

To her husband's employees, she is like an incarnation of the goddess-provider, to Jashomati she is the nurturer and to the voyeuristic exploitative priests, she is the ultimate sexual tease.

In the zamindar's "antarmahal" abounding with women resigned to their fates, she is a thinking, living, sexual being, who sets her own agendas and seeks her own pleasures, almost like a man.

She then, featured in Sekhar Das's award-winning Bengali film Krantikaal (2005), where she played the character of Subarna, who befriends a terrorist who broke into her house.

[citation needed] She acted in the much acclaimed Bengali film Ek Mutho Chabi (2005), produced by herself, where she played the character of an established actress who has a car accident, consequently losing her career.

[80][81] In December 2005, Ganguly was named by The Telegraph in the list of Five Crowning Queens of 2005 alongside Rani Mukerji, Preity Zinta, Konkona Sen Sharma and Vidya Balan.

I didn't see any point in taking payment for only five minutes of work.In 2009, she appeared in Sekhar Das's Bengali film Kaaler Rakhal.

[87] She appeared in Birsa Dasgupta's Jaani Dyakha Hawbe (2011), which after much commercial expectation proved to be a failure at the box office.

[90] She appeared in Riingo's Bengali film Na Hannyate (2012), where she played the character of Jui, who is caught in a situation where she could save only one of her kids and leave the other to die.

[99] In West Bengal Assembly elections 2016, Ganguly lost from Howrah North to Trinamool Congress counterpart and cricketer Laxmi Ratan Shukla.

[100] In May 2016, she was attacked allegedly by Trinamool Congress workers when she was returning from Kakdwip in South 24 Parganas where she had gone to meet victims of political violence.

[101] She was nominated to the Rajya Sabha in October 2016 in place of cricketer Navjot Singh Sidhu, who resigned earlier.