Thulasi was born in a Malayali family to businessman Rajasekaran Nair and Radha, a leading actress in Tamil and Telugu films during the 1980s. Her elder sister Karthika Nair is also an actress who has appeared in regional Indian films, while she also has an elder brother, Vignesh Nair. Her maternal aunt Ambika was also a contemporary of Radha's, and Thulasi has revealed she often seeks advice on acting from her mother, sister and aunt. She has juggled between completing her acting commitments and attending Podar International School in Mumbai.
At age 14, Thulasi was first considered for a role in director Mani Ratnam's Kadal in November 2011. She would feature alongside fellow debutant Gautham Karthik in the leading roles, coincidentally 32 years after her mother and Gautham's father had also debuted together in Bharathiraja's Alaigal Oivathillai in 1981. The film opened in February 2013 to mixed reviews and the film became a commercial failure at the box office. Thulasi's performance won positive reviews from critics. Her performance could fetch nominations for Best Female Debut Actress at the Vijay Awards and theSouth Indian International Movie Awards in 2014. Before the release of Kadal, cinematographer Ravi K. Chandran signed on Thulasi to appear in a leading role in his maiden directorial venture, Yaan (2014). The film released in October 2014, it received negative reviews and became a surprise failure at the box office. She also acted in Kadali, Chinni Chinni Aasa, Mr.Pellikoduku.