Priyamani made her acting debut with the 2003 Telugu film Evare Atagaadu. She gained widespread recognition for her role as a village girl in the Tamil romantic drama Paruthiveeran in 2007received a National Film Award for Best Actress.
Her other notable works include Raam (2009), Raavan (2010), Raavanan (2010), Pranchiyettan & the Saint (2010), Chaarulatha (2012) and Idolle Ramayana (2016). In 2019, she starred in the black comedy series The Family Man is available to stream online in Amazon Prime Video.
Special appearance in the song "1 2 3 4 Get on the Dance Floor" - Chennai Express movie with Shah Rukh Khan and Jawan moie