Jagapati Babu made his debut in Telugu with the movie Simha Swapnam (1989) which was directed by his father. He had his breakthrough in the form of Gaayam directed by Ram Gopal Varma in the year 1993. He won the Nandi Award for Best Actor in 1996 for his role in the movie Maavichiguru directed by S V Krishna Reddy. Two years later, he won the Nandi Award for Best Supporting Actor for the film Antahpuram. In 2000, he won the Nandi Best Actor Award for the second time for his performance in the movie Manoharam. Similarly, he bagged the Nandi Best Supporting Actor Award for the second time in the year 2007 for his role in the movie Lakshyam. His first Tamil was Madrasi, and in 2011, he appeared as the antagonist in Tamil film Thaandavam. Subsequently, he played the lead role in Jai Bolo Telangana, which won five Nandi Awards. In 2012, he debuted in the Kannada film Bachchan as a cop, which featured Sudeep in the lead role. In 2013, Jagapati Babu returned to the Tamil film industry with Puthagam and will next be seen in Rudhiram. His next movie is Legend, where he is the antogonist against actor Nandamuri Balakrishna.
He lives in Hyderabad. His views were well expressed on film industry and his personal life and in Open Heart with RK a program in ABN a Telugu news channel which was very well received by the viewers.