Kalki was born in Pollachi, a town in Tamil Nadu. Born into a middle-class family, Kalki was an academically bright student and topped her class. Kalki holds two Masters degrees: Masters in Journalism Mass Communication and Masters in International Relations. During her postgraduate studies, she started publishing a monthly magazine in Tamil for transgender women called Sahodari (which means sister).This is the first Tamil magazine published for transgender people in India. 
In 2008, Kalki founded the Sahodari Foundation, an organization that advocates for transgender people in India. In 2014, she was chosen by Facebook as one of the 12 inspiring women of the world who used Facebook for community development. Subramaniam also inaugurated Sahaj International school in 2017, which is dedicated to serving transgender students ages 25 through 50 who have not been supported in mainstream schools.  It is the first school specifically designated for transgender students in India and is located in Kochi, Kerala. The school is now closed.
In 2011, Kalki starred in the Tamil film, Narthagi, which was focused around the lives of transgender people. She made a special appearance in the 2018 film Sarkar in the song "Oru Viral Puratchi". She is the first transgender woman in India to do a lead role in a motion picture.
Kalki displayed her art at a painting exhibition in the Coimbatore, Piece by Piece. She received invitations from Germany and San Francisco to portray her work.  Her poetry titled Kuri Aruthaen (Phallus, I cut) was adopted into poetic short films titled Vadu (The Scar).
In March 2017, she was invited by Harvard Business School, Harvard University to speak on behalf of the sexual minorities, and represent the Indian transgender community.
In 2018, she was invited by Schwules Museum, Germany to present her art, poetry and activism in an Artist Talk with Professor Claudia Reiche.
She was nominated for an award in the category, Arts for Life's Sake (Arts) by NDTV Women of Worth initiative.
-  My Story, by Kalki
-  Kalki Subramaniam| About
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- "These women are so inspiring, even Facebook wants to share their stories - Mtv.com".
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- "In Conversation With A Transgender Activist And World's First Transsexual Film Star". indiatimes.com.
- "Choosing to be a woman". DNA. 15 February 2015.
- "Bhopal gets drenched in Rainbow Colours: Bhopal Pride Parade - Times of India". The Times of India. Retrieved 2018-04-25.
- "My gender is not my only identity: Kalki Subramaniam - Times of India". The Times of India. Retrieved 2018-04-25.
- "I think it's time transgenders came to power: Kalki Subramaniam - Times of India". The Times of India. Retrieved 2018-04-25.
- "Only education can empower transgenders: Activist Kalki Subramaniam". The Indian Express. 2017-01-03. Retrieved 2018-04-25.
- "Wie geht postkolonialer indischer Trans-Aktivismus heute?date=2018-11-17". Queer.de (in German). Retrieved 2018-12-01.
- "Women of Worth: About the Nominee - Kalki Subramaniam". Women Of Worth. 2016-02-12. Retrieved 2018-04-25.
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