Asin debuted in a supporting role in Sathyan Anthikkad's unsuccessful Malayalam film 'Narendran Makan Jayakanthan Vaka' in 2001, at the age of 15.

After taking a year out to pursue her education, Asin returned with her breakthrough film as an actress, 'Amma Nanna O Tamila Ammayi' opposite Ravi Teja, portraying a Tamil girl in her first Telugu language film, which subsequently fetched her the Telugu Filmfare Award for Best Actress.

In the same year she won the Santosham Best Actress Award for her performance alongside Nagarjuna in her second Telugu film, 'Shivamani'. She then acted in two Telugu films, 'Lakshmi Narasimha' and 'Gharshana, which were both solid hits.

Asin's first Tamil language film was 'M. Kumaran son of Mahalakshmi', in which she co-starred with Jayam Ravi. Asin reprised her role from her film 'Amma Nanna O Tamila Ammayi' for the remake, which saw her portraying a Malayali girl instead of the Tamil girl in the original. The movie subsequently went on to become one of the biggest hits in Tamil cinema during 2004.

After her Telugu film 'Chakram'she appeared in 'Ullam Ketkumae'.The film eventually became a successful venture at the box-office, creating wider opportunities for her.