1967–1984: Debut and breakthrough

Chatterjee made her film debut in the Bengali hit Balika Badhu (1967), directed by Tarun Majumdar.^[4] In an interview, Moushumi Chatterjee quoted: "After Balika Badhu, I was flooded with Bengali movies but I wished to complete my studies. However, movies were in my fate hence when I was studying in class X, a close aunt of mine was on her death-bed and her last wish was to see me married. Hence, to satisfy her wish I got married."^[4] She was called as Indira at home. She got engaged to guardian and neighbour Hemant Kumar's son, Jayant Mukherjee (Babu). "I fell in love with Babu. He was the first man I came in touch with outside my family."^[5] She was then seen in Bengali films like Parineeta, Anindita.

She made her debut as the leading lady in the Hindi film Anuraag in 1972 was directed by Shakti Samanta. The film proved to be a major success. She played a blind girl who falls in love, and she earned her first and only nomination for the Filmfare Award for Best Actress; Anuraag won the Filmfare Award for Best Film. About her Hindi film debut, she said in an interview: "As my father-in-law was a renowned film celebrity, many film personalities used to throng our house. One among them was filmmaker Shakti Samanta, who insisted upon me to act in movies. I declined, but both my father-in-law and my husband encouraged me, thus I got Anuraag."^[4] When asked about her first role in Hindi films she said that "[w]hen Shaktida told me that I have to play a blind lady I was taken aback. I honestly told Shaktida that I may not do justice to the role as I have never studied a blind person, but Shaktida assured me that he will take me to a blind school and train me ... he insisted to do a small Mahurat shot before. [...] When I reached the studio I was excited to see Bollywood luminaries like Nutanji, Dadamoni (Ashok Kumar fondly called), Rajesh Khanna, S. D. Burman and others. The moment Shaktida called action I did my Mahurat shot confidently and was applauded. After the shot, Shaktida told me that I had given the shot so skillfully that there was no need to visit a blind school!"^[4]

In 1973, she acted in Naina opposite Shashi Kapoor, Kuchhe Dhaage with Vinod Khanna and Us Paar with Vinod Mehra. In 1974, she acted with the then-struggling Amitabh Bachchan in the thriller Benaam and opposite Rajesh Khanna in the suspense drama Humshakal. Her most successful film came at the end of 1974, where she played a rape survivor in Manoj Kumar's Roti Kapada Aur Makaan.^[6] She received her first and only nomination for the Filmfare Award for Best Supporting Actress. She went on to become a part of several successful films like Swarg Narak, Maang Bharo Sajna, Pyaasa Sawan, Jyoti Bane Jwala with Jeetendra, Swayamvar with Shashi Kapoor and Anand Ashram with Rakesh Roshan. She acted with Rishi Kapoor in four films none of which were successful.

She was paired with Vinod Mehra in 10 films,^[7] including Anuraag, Us-Paar, Raftaar, Umar Qaid, Mazaaq, Zindagi and Do Jhoot. She only acted in 2 films with Amitabh Bachchan, Benaam and Basu Chatterjee's Manzil (1979). Her Bengali film with Uttam Kumar, Ogu Bodhu Sundari, released in 1981 and became successful. In 1982, she did the Marathi film (cameo role for song "Tumhi Adkitta Mi Ho Supari") Bhannat Bhanu. Her successful films with Rajesh Khanna included Bhola Bhala, Prem Bandhan and Ghar Parivar. She worked with Sanjeev Kumar in Angoor, Daasi and Itni Si Baat. In 1985, she acted in the Bengali film Pratigna.

After 1985, she graduated to supporting roles in several movies like Watan Ke Rakhwale, Aag Hi Aag and Ghayal.

1985–present: Transition period

From 1985 to 1991, Chatterjee got more offers as a character actress and she made the transition to roles of mother and bhabhi (sister-in-law), often pairing with Dharmendra or Sunil Dutt. She played Sunny Deol's sister-in-law in Ghayal. Occasionally, she got lead roles in films in the 1990s such as Ghar Parivaar and Aa Ab Laut Chalen, both opposite Rajesh Khanna, then Santaan, Prateeksha (1993) and Udhaar Ki Zindagi with Jeetendra. Some of her films as supporting actress since 1995 include Keemat: They Are Back (1998), Aa Ab Laut Chalen (1999) and Na Tum Jaano Na Hum, Hum Kaun Hai? (2004).

In 2006, Moushumi Chatterjee made a comeback to cinema, with Tanuja Chandra's Zindaggi Rocks. She did the Indo-Canadian production Bollywood/Hollywood in 2003.^[7]

Her Bengali films as the lead heroine include Balika Badhu (1967), Parineeta (1969), Anindita (1972), Anand Ashram (1977), Ogu Bodhu Sundari (1981), Prarthana (1984), Shatarupa (1989), Kari Diye Kinlam (1989), Bidhilipi (1991) and later as supporting actress; Nater Guru (2003), Bhalobasar Anek Naam (2005), The Japanese Wife (2010) and Goynar Baksho (2013). She sang a song titled "Tomar Duare" in the film Mallick Bari (2009). In 2014, she won the Filmfare Award for Best Supporting Actress for the Bengali film Goynar Baksho and received the Filmfare Lifetime Achievement Award in 2015.