Her paternal grandmother, D. K. Pattammal,[2] and her grand-uncle, D. K. Jayaraman,[3] were prominent Carnatic vocalists who were established disciples of Ambi Dikshithar, Papanasam Sivan, Koteeswara Iyer, T.L.Venkataramayyar and others.

Her father, an accomplished mridangist and disciple of his father-in-law Palghat Mani Iyer, constantly shows his support and accompanies her when she performs.

[13] She has given numerous concerts consisting of only patriotic songs to commemorate the 50th year of Indian Independence, a few with D. K. Pattammal before her grandmother stopped performing in public.

She has also given a lecture demonstration in Coimbatore for Manoranjitham on "Papanasam Sivan – A Legend", and made two special thematic albums that solely contained his compositions.

She presented a paper on the Life and Contribution of Gopalakrishna Bharathi for the Music Department of PSG College of Arts and Science, Coimbatore.

[7] Nithyasree Mahadevan made her debut as a playback singer after being invited by prominent music producer, A. R. Rahman to record a song for the Tamil film, Jeans.

Nithyasree Mahadevan was one among the singers who sang the "Semmozhiyaana Thamizh Mozhiyaam" song for the World Classical Tamil Conference 2010.

She also appeared as a guest judge on episodes 22 and 23 of Indian Voice which was aired in October 2012 on Mazhavil Manorama, a Malayalam language TV channel, and as a guest judge for the finals of season 6 of Raj TV's Raja Geetham,[21] which was held on 6 August 2015 at Kamarajar Arangam,[22] and subsequently aired on 15 August 2015.

[22] Nithyashree appeared as a special guest for the debut season of Zee Tamil's Sa Re Ga Ma Pa Lil Champs.

She sang several advertisement jingles for various companies, including more recently Sree Kumaran Thangamaligai which was recorded and aired on various Tamil language TV channels.