He did his schooling at St Bede’s School in Chennai and obtained a degree in commerce from Loyola College, Chennai

He married Bollywood actress and former Miss India Namrata Shirodkar on February 10, 2005, and has a son Gautham Ghattamaneni (born in 2006).

Mahesh Babu started out his movie career as a child actor in his father's films. His debut was in Raja Kumarudu, starring opposite Preity Zinta, and he won the Nandi Award for Best Male Debut. In 2000, he starred in Yuvaraju. In the same year, he shared screen space with Namrata Shirodkar and his father Krishna in Vamsi. Murari in 2001 with Sonali Bendre, was directed by Krishna Vamsi, and won him a Nandi Award - Special Jury. He won the award again in 2002 for Takkari Donga which is a cowboy movie. In 2002, he starred in Bobby opposite Arthi Agarwal. In 2003, he acted in Gunasekhar's Okkadu with Bhoomika Chawla. His performance in Okkadu won him the Filmfare Best Telugu Actor Award. His next movie, Nijam, won another

He acted in Nani under the direction of S. J. Suryaah. Another Nandi Award for Special Jury went his way for his role in Arjun acting with Shriya Saran. Athadu in 2005 broughtanother Nandi - Best Actor Award. The 2006 release Pokiri won him the Filmfare Best Telugu Actor Award for his portrayal in lead role. He has one more release Sainikudu under the direction of Gunasekhar in the same year (2006) followed by Pokiri which was dubbed in Tamil. He paired up with Trisha in Sainikudu. Athidi with Amrita Rao released in 2007 was produced by his brother Ramesh Babu which was taken by UTV motion pictures and dubbed in Tamil. In the year 2008, he gave voice over to the film Jalsa.

After not working nearly for more than an year, Mahesh Babu signed a project in late 2009 Called Kaleja under the direction of Trivikram Srinivas. In 2009, he also signed as a brand Ambassador for the Univercell mobile phones and services. He has signed a film with Srinu Vaitla. The tentative title of the film is going to be 'Dookudu'. He has also signed a movie with Surender Reddy, which will go on sets in the middle of next year. The film's tentative name is 'Mr.Perfect'. He has also signed another movie with Arya 2 fame director Sukumar. He also has another movie which is not confirmed with new director Venu Sriram. He had a long discussion with S.S. Rajamouli and finally they had decided to do a movie together. The movie might take a while to go on sets as Mahesh and Rajamouli are busy with their latest projects. And On April 6, 2010, Mahesh started using Twitter in order to better interact with his fans and well wishers.

Mahesh Babu is the other name for adventurous fights and hollywood range acting. He is the only actor who got many awards in past 10 years than any other actor. He is currently doing the final stage of Trivikram's movie which is set to release in September.His has signed a movie with Srinu Vytla and its going onto sets from 20 July 2010.