Akshaye's first debut movie was as an actor when he was 21 years old in the 1997 in his father's production Himalayputra which flopped at the box office. Akshaye Khanna has since demonstrated a versatility with a wide array of roles in a string of successful films. His first box office success was J.P Dutta's Border (1997) followed by Subhash Ghai's Taal (1999) and Farhan Akhtar's Dil Chahta Hai (2001) for which he won Best Supporting Actor. With his first negative role in Humraaz (2002), Akshaye's performance was applauded and earned a nomination for Best Villain. Akshaye recently has ventured into the low concept comedies of Priyadarshan such as Hungama (2003) & Hulchul (2004) and has enjoyed success there as well.

In 2006 his first three releases, Shaadi Se Pehle, 36 China Town and Aap Ki Khatir have not done as well as expected at the box office. His recently released film was Nikhil Advani's multi-starrer, Salaam-e-Ishq: A Tribute To Love which released on January 25, 2007. Although much hyped, the film failed to do well. This was followed by the suspense thriller Naqaab which didn't do that well. Akshaye's recent portrayal of Harilal Gandhi in the critically acclaimed, Gandhi, My Father was praised by critics and was mentioned as his best performance so far.