She started her acting career with the Malayalam film Neram Pularumbol. Although this was the first movie where she acted, it had a delayed release in 1986. Her first release was Vellai Manasu in 1985, a Tamil movie opposite Y. G. Mahendra. Her first Telugu film was Bhalae Mithrulu (1986). Then she went on to play supporting roles in Tamil films which include Padikkadavan (1985) starring Rajinikanth where she was given a uncredited role and Per Sollum Pillai (1987) starring Kamal Haasan. In Telugu, she starred with Rajendra Prasad in Madana Gopaludu (1987), Bhama Kalapam (1988), Asthulu Anthasthulu (1988) and Bava Marudula Saval (1988). She worked in Malayalam films such as Orkkappurathu, Aryan and Anuragi with Mohanlal. She enjoyed success in Kannada movies as well. One of her earlier roles as heroine was in Krishna Rukmini opposite superstar Vishnuvardhan. She played a small role in the Hindi film Dayavan that starred veteran actor Vinod Khanna.[6]
Comeback to Tamil cinema and debut in TV serials (1999–2009)
After a four-year break from Tamil cinema, in 1999, Ramya played the female antagonist in Padayappa opposite Rajinikanth. The critic from Rediff stated "Ramya does a fantastic job. She is vicious to her dying breath, when she declares she will revenge herself in her next life. She does a fabulous tandav of rage when her father commits suicide".[7] She went onto receive several awards including Filmfare Award for Best Actress - Tamil and Tamil Nadu State Film Award Special Prize. She then starred in commercially successful films like Budget Padmanabhan and Panchatanthiram. The critic from Screen called her performance in Panchatanthiram "one of the finest performances ever".[8]
Ramya has also acted in many devotional films including Rajakali Amman (2000), Nageswari (2001), Sri Raja Rajeshwari (2001) and Annai Kaligambal (2003).
The Vice-President, Venkaiah Naidu giving away a special award to film artiste, Ramya Krishnan, at the 30th Ugadi Celebrations & Puraskar Presentation - 2018, organised by Delhi Telugu Academy, in New Delhi
She made her debut in the digital platform with Queen in 2019.[14] The critic from India Today stated "Ramya Krishnan as the failing actress and a budding politician (the later part of Shakthi's life) puts in a measured performance and it is what stands out in a series that relies heavily on performances".[15] In 2022, Ramya appeared in Dharma Productions and Puri Jagannadh's sports action film Liger.[16]