Raai Lakshmi made her debut at the age of 15 in the Tamil film Karka Kasadara in 2005. Subsequently, she appeared in a number of Tamil films, including the comedy film Kundakka Mandakka (2005) opposite R. Parthiban, Perarasu's action-masala flick Dharmapuri (2006), and the romance film Nenjai Thodu (2007). In 2008, she began working in more serious films such as the drama film Velli Thirai, in which she played herself, and the action thriller Dhaam Dhoom directed by Jeeva. She received positive feedback for her portrayal of a lawyer in the latter. A review from Behindwoods wrote: "The latter (Raai Lakshmi) sizzles even as she is supposed to play the court professional who is caught in the web of smuggling drugs".
Raai Lakshmi's first 2011 release was Christian Brothers, which was a huge commercial success. Her next two films were Tamil projects, the comedy horror Kanchana and the Venkat Prabhu-directed action thriller Mankatha, starring Ajith Kumar. She played a negative character in the latter, which was received positively by critics. Both films emerged as high financial successes. Following Kanchana's success, she was signed on to reprise the role in its Kannada remake. Based on an online poll conducted by The Times of India, Raai Laxmi won the "Best Actor Award in a Negative Role - Female" for Mankatha.
She made her Bollywood debut with the film Akira in 2016. She will be seen in upcoming Hindi film Julie 2.