Vyjayanthimala was born to M. D. Ramaswamy and Vasundhara Devi, who was a actress and dancer. At the age of five, Vyjayanthimala was chosen to perform a classical Indian dance for Pope Pius XII while her mother was an audience in 1940 at Vatican City. She did her schooling from Sacred Heart Higher Secondary School, Presentation Convent, Church Park, Chennai. She learned Bharata Natyam from Guru Vazhuvoor Ramiah Pillai and Carnatic music from Manakkal Sivaraja Iyer. She had her arangetram at the age of 13. Her maternal uncle is Y. G. Parthasarathy.
She made her film debut in Vazhkai. The movie was a big success and was remade in Telugu after one year as Jeevitham and also remake it in Hindi as Bahar in 1951. The film became sixth highest grossing film of 1951 with a verdict of box-office hit. After the success of her debut films in all three languages, Vyjayanthimala again acted in multilingual film which was produced by Avichi Meiyappa Chettiar of AVM Productions. The first version was in Tamil as Penn and in Telugu titled Sangham. The Tamil and the Telugu films were big successes across South India. The film was once again remade in Hindi as Ladki. The movie became second highest grossing film of 1953. Vyjayanthimala debuted in Kannada cinema through a film called Asha Nirasha which was produced by G. D. Venkatram, but the movie was unreleased. In the same year, she also acted in swashbuckler film Devta which was a remake of a hugely successful Tamil film Kanavaney Kankanda Deivam. Vyjayanthimala then acted n the comedy film New Delhi which became the fifth highest grossing film of 1956 a box-office hit. Subsequently, she did a Tamil film Marma Veeran. In 1957, director B. R. Chopra made Naya Daur, received positive reviews from critics. At the end of its theatrical run, the film had collected around 54,000,000, thus becoming the second highest grossing film of 1957, second only to the critically acclaimed Mother India which became the highest grossing Bollywood film ever at the time. The following year proved to be very successful for Vyjayanthimala where she signed opposite Dilip Kumar in Bimal Roy's Madhumati in the title role. The film was well received by critics and audience where it became highest grossing Bollywood film of 1958 and was labelled as blockbuster at box office and ended up as fifth highest grossing film of the decade with its adjusted inflation net gross to about 586.4 million. The film later inspired films such as Milan, The Reincarnation of Peter Proud, Mehbooba, Kudrat, Karz. Karan Arjun and particularly Om Shanti Om. Vanjikottai Valiban was followed by its Hindi version titled Raj Tilak. Screenplay of the film was by Ramanand Sagar. Within a week, the film sank at box office and was unable to achieve the same box office success made by the Tamil version. In 1959, Vyjayanthimala reunited with Dilip Kumar for the fourth time in bilingual Paigham. Upon release Paighambecame second highest grossing film of 1959 with a verdict of a box-office hit. The same year she did a Tamil film, Athisaya Penn where she co-starred with Telugu actor Akkineni Nageswara Rao for the first time. Athisaya Penn was a remake of Aasha which again was directed by M. V. Raman. Her first release in 1960 was S. S. Vasan's Irumbu Thirai, the Tamil version of Paigham. Her subsequent release was D. Yoganand's magnum opus Parthiban Kanavu. Co-starring Gemini Ganesan for the third time and B. Saroja Devi for the second time, the film was based on Kalki Krishnamurthy's 1942 novel with the same name. Apart from Tamil, the film was produced in Telugu and Sinhala languages. Upon release the film met with positive response from the critics. Meanwhile, she did a Hindi film titled College Girl opposite Shammi Kapoor which fared average at box office and was declared as eighteenth highest grossing film of the year. In 1968, Vyjayanthimala appeared in three big budget film with high profile actors such as Dilip Kumar, Dev Anand and Rajendra Kumar. Sunghursh was followed by Saathi directed by C. V. Sridhar. Remake of highly acclaimed Tamil film of 1961, Palum Pazhamum. All her releases in 1968 did not enjoy success at the box office. Duniya, Saathi and Sunghursh was named as tenth, eleventh and twelfth highest grossing film of 1968 respectively, with the first two was labelled as average while the latter only managed to do above average business at box office. Vyjayanthimala married Chamanlal Bali in 1968. After marriage, she gave up her acting career and moved to Chennai. They have a son, Suchindra Bali. In 2007, she published her autobiography, titled Bonding, with Jyoti Sabarwal as co-writer. Post her retirement in films, Vyjayanthimala was offered with many roles by big banners opposite leading actors of that time. But she refused all those offers as she does not want to make a comeback. She also involved in politics.