In 2013, the Government of India announced the Padma Bhushan award for her, at the age of 74. The singer refused to accept the award, because it came too late and because South Indian artists weren't given their due recognition. She is honoured by those people, who like to hear her voice, instead.

S. Janaki was born in a Telugu speaking Brahmin family in Pallapatla, Repalle village, in Guntur, Andhra Pradesh. Her father Sishtla Sreeramamurthy was a teacher and an Ayurveda doctor. Her father worked in Sircilla in Karimnagar district. She was interested in music from an early age and started performing at the age of three. She learned music from Sree Paidiswamy, a Nadaswaram Vidwan for only one year. She also learned a few songs from Varanasi Balaramayya in Kovvur. She was inspired from film music and used to render the songs of Lata Mangeshkar, P. Leela, Jikki and P. Susheela on stage before entering films.

S Janaki started singing in movies at the age of 19. She later moved to Chennai on the advice of her uncle Chandrashekar and joined AVM Studios as a singer. She started her career in movies by singing songs composed by T. Chalapati Rao in the Tamil movie Vidhiyin Vilayattu in 1957. Subsequently, she performed in the Telugu movie MLA. "Singara velane deva" made her singing star over night. She sang several memorable duets with P B Srinivas and occasionally with T M Soundarrajan, A M Rajah & Ghantasala during the 1960s. Janaki became one of the most preferred female singers of South India from early 1970s due to her renditions of compositions of M.S.Vishwanthan from 1960's and 1970's - from the films - Alaymani,Alaigal, Avalku Endra Oru Manam, Namma Kuzhandhaigal,Thangaikkaga,Sudraum Sooravalium, Ganga Gowri and the duet song Konjam Neram from the MGR film Sirithu Vazha Vendum with T M Soundarrajan established Janaki as famous singer in early 1970's in Tamil films and thereafter every music director from Tamil film insustry started making her sing in their films. Then from 1976, Janaki went on to become one of the most favorite singers of Ilayaraja, and a phase ensued when she sang at least 2 to 3 songs per movie in all the four South Indian languages.

She sang in almost every major South Indian movie in from 1976-1999. From the 1980 till 1999, she was the top female singer in south Indian films and was the 2nd top female singer after P.Susheela from 1970-1980. She won several awards from government and private institutions during this period. She has a record of maximum singing compared to any other female singer in the Malayalam and Kannada film industry and she also holds the record of singing the most difficult song in South Films i.e. Shiva Shiva Ennada from the Kannada movie Hemavathi.

S Janaki started being noticed by all in Malayalam industry from early 1960s. M S Baburaj reserved his best compositions to her and made her a house hold name in Kerala. Their combination brought great melodies which stood test of time. She went on to record hits for M B Srinivasan, M S Viswanathan, Johnson, Ravindran, Dakshinamurthy, M K Arjunan, A T Ummer, Shyam and many others. Her duets with K J Yesudas, P Jayachandran topped the charts and remained as all time hits. She won awards almost every year for a decade in Malayalam. She remained as undisputed melody queen of Malayalam film industry from late 1960s to late 1980s.

Her career in Kannada industry was equally, if not more successful. She reigned the Kannada music till late eighties. She continued to give some hits in 1990s as well. She was present in almost every album of G K Venkatesh and Rajan Nagendran. M Rangarao, Upendrakumar, Vijayabhaskar also gave her excellent melodies. Hamslekha used her singing talent in several albums, which were huge hits. Her duets with S P Balasubramanium, PBS and Rajkumar are immensely popular till date. Rajan Nagendra-SPB-Janaki is considered to be the most successful team to produce several unforgettable duets in Kannada.

While speaking about her career, her contribution to Telugu and Tamil cinema cannot be ignored. Though she was singing from late 1950s and delivering hits in these languages, popular songs in combination of M S Viswanathan brought her a lot of fame and recognition in late 60's and early 1970's. She became nationally famous from 1976 due to her teaming up with Ilayraja. Her vocal skills were tested to the core and she won every time in songs by Ilayaraja. Her smile/laugh, sensuous notes, alaaps/humming were used to a major extent. Other music directors like Chakravarthy, Sathyam, Ramesh Naidu, M S Viswanathan, K V Mahadevan, Shankar Ganesh in 1980s to give some of their career best melodies to Janaki. She rendered several semi-classical numbers also with lots of ease during this period. She delivered several hits with SP Balasubramanyam, Malaysia Vasudevan, K J Yesudas, Jayachandran, Mano, Arunmozhi in Tamil. She also sang super hit duets with actors like Kamal hasan, Rajni Kanth etc. Her duets were very popular and some of them were major reasons for the success of several movies. She continued to deliver hits with the younger generation of music directors like Madhavapeddi Suresh, Vandemataram Srinivas, Raj-Koti, Deva, S A Rajkumar, Yuvan Shankar Raja etc. in the 1990s and after 2000. She also sang few songs in music of A R Rahman and they were very popular.

She was invited to Hindi film industry by Bappi Lahiri for the 1985 movie Saheb, where she delivered super hit "Yaar Bina Chain Kahan Re". She sang around 100 songs in the music of Jaidev, Lakshmikant Pyarelal, R D Burman, Ravindra Jain, O P Nayyar, Bappi Lahiri, Anu Malik and others. She recorded duets with Mohd Rafi(in Telugu movies), Kishore Kumar, Manna Dey, Bhupinder, Manhar Udas, Amit Kumar, Suresh Wadkar, Mohd Aziz, Udit Narayan, Shankar Mahadevan and others. But she personally preferred singing south Indian songs as she was getting melodious songs with better quality at that time than in Hindi.In Hindi her duets with Kishore Kumar were the most pupular - like Mamla Gadbad Hai from Dharmadhikari, Pyar Ki Pehli Raat from Sighasan, Galon Par Jab Aise from Masterji, Main Tera Tota from Paap Ki Duniya.

She also penned many songs for Tamil and Telugu albums as she was extremely good in both the languages. She has also sung in Sinhalese, Bengali, Oriya, English, Sanskrit, Konkani, Tulu, Saurashtra, Baduga, Japanese and German.

As a devotee of Lord Krishna and Shirdi Sai Baba, she has also recorded Hindu devotional music of Meera. She released albums with songs of Meera, Tulsidas, Surdas & Kabir Das. She released 3 classical albums with songs of Thyagaraja Swamy, Muthuswamy Deekshithar and Swathi Thirunal. She has sung Devaranamas of Purandara Dasa and worked for restoring Ramadasa Keertanalu. She worked with Balakrishna Prasad and sang some of the finest anamacharya keerthanas for him. She rendered several devotional albums apart from these classic albums. She has sung for television and radio programs as well and won awards for best playback from Andhra Pradesh state government for TV Serials.

Her contemporaries include Malaysia Vasudevan, S.P.Balasubramanyam, P B Srinivas, Rajkumar, Ghantasala, T. M. Soundararajan, P. Susheela, Vani Jayaram, K J Yesudas, L R Eeswari, P. Jayachandran, P. Leela, K. S. Chithra, Uma Ramanan, Swarnalatha, Sujatha, Hariharan, Unni Krishnan, Srinivas, Unni Menon and Jency

S. Janaki was married to V. Ramprasad. She is now settled in Chennai with her son Murali Krishna, who acted in a few films and has an audio business of his own, and his wife Uma Murali Krishna, a classical dancer (Bharatnatyam and Kuchipudi); they have two daughters named Amruthavarshini and Apsara. She is also a close relative of Carnatic classical vocalist Garimella Balakrishna Prasad.