Born on 25 August 1973 to Lalitha Sivakumar and I. Sivakumar, Nithyasree Mahadevan (previously known as S. Nithyashri) hails from a musical lineage of Carnatic music veterans. Her paternal grandmother, D. K. Pattammal, and her granduncle, D. K. Jayaraman, were renowned Carnatic vocalists while her maternal grandfather was the mridangam virtuoso, Palghat Mani Iyer. A prominent Carnatic music vocalist and playback singer for films, Mahadevan has performed in all major sabhas in India and at prestigious events all over the world. 

She was initiated into music by her mother, who was also her first guru. Consequently, she also underwent training with her grandmother, D. K. Pattammal, and would accompany her in concerts. Her father, an accomplished mridangist himself, was a source of encouragement and inspiration, accompanying her when she performed. 

Mahadevan's first Carnatic performance was for the Youth Association for Classical Music on 10 August 1987 and was attended by distinguished musicians. Her maiden performance was titled 'best concert of the series'. She is an AIR Prize Winner (1990) and has been an 'A' grade artist. She has received several awards and honours in recognition of her talent and contribution to Carnatic music including the ‘Yuva Kala Bharathi’ title by Bharath Kalachar in 1994, ‘Innisai Maamani’ by Tamil Nadu Welfare Association, ‘Kalaimamani’ by Tamil Nadu Government in 2000, ‘Isai Paeroli’ by Kartik Fine Arts in 2001, ‘Padma Sadhana’(2004), and ‘Naada Kovida’ (2006). She also holds an honorary doctorate degree from Sathyabama University of Jeppiar in Chennai. 

Mahadevan is known for her distinct, high-pitched voice that adapts easily to a variety of genres. On 3 February 2013, on the occasion of the Thyagaraja aradhana (anniversary) at the TTK auditorium of The Music Academy, Chennai, she returned to on-stage performance after passing through a traumatic phase in her life (the untimely death of her husband Mahadevan on 20 December 2012). She was led and accompanied by her friend and veteran singer S. Sowmya. 

Mahadevan's foray into Tamil playback singing can be traced back to the 1990s when she first recorded for music director A.R. Rahman’s song ‘Kannodu Kanbadellam’ in the movie Jeans starring Aishwarya Rai and Prashanth.