Breakthrough, 2005 - 2007

After the release of Ullam Ketkumae, Asin became publicized as a leading heroine after signing films with the four leading actors of the Tamil industry: Surya, Vikram, Vijay and Ajith in Ghajini, Majaa, Sivakasi and Varalaru respectively. The venture which provided the breakthrough for Asin to become the leading South Indian actress was her Tamil film, Ghajini. The film, co-starring Surya and Nayantara and directed by A. R. Murugadoss, helped Asin secure the Tamil Filmfare Award for Best Actress. Her role, that of a vivacious young model called Kalpana who dies, became a trendsetter and was parodied in several other films after the release of Ghajini. Sify.com praised her portrayal as "magical" and that "Kalpana was the lovable chatterbox, [with] sheer ability in the romantic interludes, the poignant and heartfelt scenes when she rescues minor girls from villains and her gory end are touching". The reviewer further went on to mention that "The chemistry between the lead pair in the first half is a delight", a view that became common among film producers who attempted to put their pair opposite each other for the films, Sillunu Oru Kaadhal and Vaaranam Aayiram, both of which started without Asin. The following Diwali in 2005, Asin had two big releases in Sivakasi and Majaa. Despite the latter becoming an average grosser, the former also went on to be a successful venture at the box office, despite Asin's poorly etched out role.

The following year, Asin opted for a less hectic schedule, becoming more choosy with her roles, rejecting several opportunities in the process. Her long-delayed venture, Varalaru opposite Ajith Kumar, became the biggest blockbuster of 2006 in Tamil cinema, after releasing for Diwali 2006. The film's hero-centric plot retreated Asin to the sidelines, but her role was well acclaimed by critics. Asin kept intact with her popularity in Telugu films by appearing in Pawan Kalyan's Annavaram, another successful venture in hwich she had a poorly-etched out role. In January 2007, Asin appeared opposite Ajith Kumar and Vijay in two different films, Aalwar and Pokkiri, with the latter becoming a super success, whilst Aalwar became a failure. The two projects which released on the same day, had been billed up as rival films due to the rivalry of the lead actors in the films. Whilst Asin's role in Aalwar was criticized, her performance in Pokkiri was lauded by critics. Her final project of the year was opposite in Hari's Vel, which had a Diwali 2007 release, subsequently becoming her third successful film which released during the Diwali season in three years. The film saw Asin and Surya put apart their creative differences and appear alongside each other after Ghajini. Asin, who portrayed a TV anchor, was appreciated for her role in the film.