Nayanthara was born in Bengaluru, Karnataka, India, to Malayali Orthodox Christians parents Kurian Kodiyattu and Omana Kurian who hail from an ancestral family Kodiyatt in Tiruvalla, Kerala.

Nayanthara did her schooling in Jamnagar, Gujarat and Delhi.

In Tiruvalla, she studied at Balikamadom Girls Higher Secondary School and then attended Marthoma College for her bachelor's degree in English Literature.

She made her acting debut in the 2003 Malayalam film Manassinakkare and followed with Vismayathumbathu (2004) before foraying into Tamil and Telugu cinema.

She made her debut in Tamil cinema in 2005 with Ayya and a year later in Telugu with Lakshmi, after which she was the female lead in numerous commercially successful Tamil and Telugu films.

In 2010, she also made her Kannada film debut through the Kannada-Telugu bilingual film Super.

Her portrayal of Sita in Sri Rama Rajyam (2011) earned her the Filmfare Award for Best Telugu Actress and the Nandi Award for Best Actress.

She won the Filmfare Award for Best Tamil Actress for her performance in Raja Rani (2013).

Kochi Times listed her in the "List of 15 Most Desirable Women in 2014".

With a series of successful films like Thani Oruvan, Maya and Naanum Rowdy Dhaan (2015), she became the highest paid actress of South India.

Nayanthara started dating actor-director Prabhu Deva in 2008. In 2010, Prabhu Deva's wife Latha filed a petition at the family court, seeking directions against Deva from live in relationship with Nayantara and requesting a reunion with him.