Chiranjeevi began his acting career in 1978 with Punadhirallu. However, Pranam Khareedu was released earlier at the box office. In 1987, he starred in Swayamkrushi which was dubbed into Russian and was screened at the Moscow International Film Festival. Chiranjeevi won the 1988 Indian Express Best Actor Award and the state Nandi Award for Best Actor awards for his performance in the film. In 1988, he co-produced Rudraveena which won the National Film Award for Best Feature Film on National Integration.

     Chiranjeevi's 1992 film Gharana Mogudu, directed by K. Raghavendra Rao, is the first Telugu film to gross over ₹10 crore (equivalent to ₹62 crore or US$8.7 million in 2019) at the box office. The film was screened at the 1993 International Film Festival of India in the mainstream section. It made him catapult  to the cover pages of national weekly magazines in India. The entertainment magazines Filmfare and India Today named him "Bigger than Bachchan", a reference to Bollywood's Amitabh Bachchan. In 2002, Chiranjeevi was given the Samman Award for being the highest Income Tax payer for the 1999–2000 assessment year by the Minister of State for Finance. A poll conducted by CNN-IBN in 2006 named Chiranjeevi the most popular star of the Telugu film industry. In 2006 he was conferred Indias Third highest civilian honour Padma Bhushan. In 2022 he was given the 'Indian Film Personality of the Year' award at 53rd Interntional Film Festival of India. In 2024 he was conferred Indias Second highest civilian honour Padma Vibhushan.

     In 2013, he inaugurated the Incredible India Exhibition, a joint participation of the Ministry of Tourism and Ministry of Information and Broadcasting at the 66th Cannes Film Festival. Chiranjeevi represented Incredible India at the 14th International Indian Film Academy Awards ceremony held in Macau. In 2013, IBN LIVE named him as one of "the men who changed the face of the Indian Cinema".