Meghana Raj debuted as a theater artist, when she was a child, acting alongside her father Sunder Raj in the play Jokumaraswamy. During the audio launch function of the Tamil film Poi in February 2006, she was invited by its director K. Balachander to pursue an acting career, starring in one of his forthcoming films. Accepting his offer, she was given the lead female role in the Tamil film Krishnaleelai, a Balachander production, directed by Selvan.^[5] However, despite continuing shooting throughout 2008, which was completed in early 2009, the film got stuck in production hell, and its release got delayed for various reasons.

Even before the release of that film, she commenced shooting for a Telugu film Bendu Apparao R.M.P, which would eventually be her first feature film release. She played the character of a school teacher in the comedy entertainer, starring Allari Naresh and Kamna Jethmalani as well, which released in October 2009 and went on to become highly successful at the box office.^]She debuted in the Kannada films by enacting the female lead role in Punda, a remake of the 2007 Tamil film Polladhavan. Meghana's next release was her debut Tamil film, the Boopathy Pandian-directed Kaadhal Solla Vandhen, which was a commercial failure, while she also signed up her first Malayalam project, the horror film Yakshiyum Njanum under Vinayan's direction, which was released in August 2010.The film was an average grosser, but its glamorously picturized songs on Meghana was a hit among the youth. During that time she also acted in two more Tamil projects, Nandha Nanditha, which is a remake of the 2008 Kannada film Nanda Loves Nanditha and Kalla Siripazhaga.