Divya Spandana stepped into the Kannada film industry as Ramya with the film Abhi starring against Puneet Rajkumar. Subsequently, she acted in many Kannada films, enacting the lead female role, establishing herself as one of most-sought after actresses in the Kannada film industry. Arasu with Puneet Rajkumar and Meera Jasmine was a huge hit.
In 2004, Spandana debuted in the Tamil film industry, also under the name Ramya, with the film Kuthu alongside Silambarasan, which managed only a mediocre run at the box office as did her next Tamil film Giri. Her debut film, however, gave her the name 'Kuthu' Ramya, by which she was popularly known in Tamil Nadu. Her breakthrough in Tamil came through her film Polladhavan, where she acted against Dhanush. The film, released during the 2007 Deepavali period, was considered a dark horse success. Rajinikanth was all praises for the entire crew of Polladhavan.
She also worked in Gautham Menon's Vaaranam Aayiram opposite Surya Sivakumar. She changed her screen name to her actual name Divya, which is believed to have brought her more luck in getting hi-fling roles. She had also dubbed in her own voice for Vaaranam Aayiram.
She is currently shooting for Singam Puli opposite Jeeva and Kadhal 2 Kalyanam alongside a newcomer Sathya in Tamil and Kicha-Hucha. Her kannada film Mussanjemaatu with Sudeep was a big hit, for which she also received a nomination for a Filmfare Award for Best Actress. She didn't have any releases in 2009. Her first movie of 2010 Just Math Mathalli which released on January 26th, 2010 was a huge success and it also received rave reviews. Her role in the movie was also very much appreciated. Her next project is Sanju weds Geeta opposite Srinagar Kitty. She is also the brand ambassador for Royal Challengers Bangalore.