She is best known for earning a National Film Award for Best Actress for her role in the 2006 Tamil film Paruthi Veeran directed by Ameer Sultan. She is the cousin of Bollywood actress Vidya Balan.
Priyamani made her debut in her native film industry, Malayalam, through the film Satyam where she starred opposite another rising actor Prithviraj.
In 2008, she paired again with prithviraj for film Thirakkatha which won huge critical acclaim for her role, in which she played a role based on the turbulent real life story of late film actress Srividya.
Priyamani is being paired for the third time with good friend and actor Prithviraj Sukumaran for her next Tamil film Ninaithale Inikkum, which is a remake of Malayalam blockbuster Classmates.
Her biggest project in the pipeline happened when she was hired by ace Indian director Mani Ratnam for his next bilingual film Ashokavanam. Priyamani's co-stars in the film include Prithviraj Sukumaran, Vikram and also former Miss World Aishwarya Rai.