Ishaa Koppikar's career started in Kollywood, where she was paired opposite Prashanth in Kaadhal Kavidai. A lot of the film was shot in London and became a blockbuster following its release, winning the lead actors rave reviews and Koppikar winning the Filmfare Best Female Debut (Tamil). With this, Ishaa was touted to be the next non-Tamil girl after Simran Bagga,who would take over the Tamil film industry. Her second movie was the highly-anticipated Tamil film, En Swasa Katre opposite Arvind Swamy, one of the most successful actors at that time. The film was a musical hit, rendered by A. R. Rahman, and a good grosser at the box-office. She then played a cameo in Prashanth's Jodi as a prospective bride. She received positive reviews for her role and decided to pursue a career in Bollywood: Her first Hindi movie was Ek Tha Dil Ek Thi Dhadkan (1997), directed by Shah Rukh Sultan, and yet to be released.

Koppikar appeared in minor roles in Fiza (2000), Pyaar Ishq aur Mohabbat and Aamdani Atthanni Kharcha Rupaiya (2001). In 2002, she appeared in Ram Gopal Varmas Company as an Item girl in the song Khallas!. The number created her nickname Khallas-girl and caused her breakthrough. In 2003 she won 'Most Exciting New Face' for Khallas at the Stardust Awards. In Dil Ka Rishta she played opposite Aishwarya Rai and Arjun Rampal and for her negative role in Qayamat: City Under Threat (2003), she received a nomination for Filmfare Best Villain Award. In the movie Girlfriend (2004), she played a woman involved in a lesbian relationship. For the role she built up her body to display some impressive muscles and performed her own stunts and fight scenes. In D (2004), she again worked with Ram Gopal Varma in the prequel of his movie Company.

In 2005 she played Arshad Warsi's girlfriend in the Salman Khan starrer Maine Pyar Kyun Kiya?. In the same year she appeared opposite Anupam Kher and Tusshar Kapoor in the comedy Kyaa Kool Hai Hum. For her role as policewoman Urmila Martodkar she received three award nominations for best comedy.

Farhan Akhtar directed a 2006 remake of the Amitabh Bachchan hit Don: The Chase Begins Again, this time with Shahrukh Khan in the lead. Koppikar was cast as Khan's moll Anita. By now the success of Don was in contrast to Koppikar's stuttering career with a string of films stuck in production or abandoned. Vicky Ranawat's Haseena Smart Sexy and Dangerous crept out towards the end of 2006, Jagdish A Sharma's murder mystery Garhee appeared on dvd, Hansel Mehta's Raakh was dropped, whilst Koppikar's highest profile film of 2007, Nikhil Advani's multi starrer Salaam-e-Ishq, saw her sharing limited screen time with Sohail Khan. Ram Gopal Varma's much discussed Shabri, directed by Lalit Marathe -a role which led to Koppikar being unrecognised in character and barred from the film set by secuirty men- has yet to attract a distributor. To date only Ram Gopal Varma's Darling, with Fardeen Khan and Esha Deol has seen Koppikar continue any kind of momentum. Atul Agnihotri's Hello, based on the novel One Night in a Call Centre by Chetan Bhagat, has a 2008 release date and may be the first of several new movies which include Jahnu Barua's Har Phall, Manoj Tiwari's Hello Darling, Right Ya Wrong by Neeraj Pathak and Kaushik Ghatak's Ek Vivaah Aisa Bhi.