The Goa Governor, B.V. Wanchoo, the Chief Minister Manohar Parrikar and Balakrishna were seen along with award winners and other dignitaries at the closing ceremony of the 43rd edition of the IFFI. Balakrishna, in his speech, said that although the Telugu film industry finds no place in the film festival by way of representation to its films, 80 percent of the movies that are produced in India are in regional languages, out of which 50 percent are from South India. "Today, film industry is facing competition from radio, and television as also from piracy," he stated. He also maintained that the film festivals have enlarged his vision towards his career.

Balakrishna was born in 1960 in Chennai (then Madras), Tamil Nadu to Telugu actor and three-time former Chief Minister of Andhra Pradesh Nandamuri Taraka Rama Rao and his wife Basava Tarakam. As the Telugu film industry was based in Madras at the time, he spent his entire childhood in Madras. During his adolescence, he moved to Hyderabad following the shifting of the Telugu film industry to that city. He earned a bachelor's degree in commerce from Nizam College, Hyderabad, Telangana. In 1982, at the age of 22, he married Vasundhara Devi.

In 1974, Balakrishna acted as a child Artist in Tatamma Kala, which was directed by NTR. Over a period of time, he acted in several films, many of which were directed by NTR. Out of which Dana Veera Soora Karna, Sri Madvirata Parvam, Akbar Salim Anarkali and Sri Tirupati Venkateswara Kalyanam became memorable films in his film career. His roles as Abhimanyu in Dana Veera Soora Karna, Sri Madvirata Parvam and Salim in Akbar Salim Anarkali and saint Narada in Sri Tirupati Venkateswara Kalyanam are highly praised. At the age of 16, he acted in a movie titled Annadammula Anubandham, a remake of Dharmendra's Hindi movie Yaadon Ki Baaraat. After watching this movie, another legend of Tollywood Akkineni Nagewara Rao commented that" "Simham kadupuna sihame puttindi". In this film, Balakrishna appeared in a brother role to his real life father NTR. Balakrishna appeared as son to his real life brother Nandamuri Harikrishna in the movie Dana Veera Sura Karna.

On the other hand, Balakrishna is known for his works in biographical films, historical films, and hagiographical films. He essayed poet Vemulawada Bheemakavi in Vemulawada Bheemakavi (1976); as Abhimanyu in Daana Veera Soora Karna (1977); as Jahangir in Akbar Salim Anarkali (1979); as Narada in Sri Tirupati Venkateswara Kalyanam (1979); as Sidda in Srimadvirat Veerabrahmendra Swami Charitra (1984) screened at the Moscow Film Festival; as Krishnadevaraya in Aditya 369 (1991), screened at the International Film Festival of India; as Satya Harischandra and Dushyanta in Brahmashri Vishwamitra (1991); as lord Krishna, and Arjuna in Shri Krishnarjuna Vijayam (1996); as Pundarika in Pandurangadu (2008); as lord Rama in Sri Rama Rajyam (2011); which received special mention at the International Film Festival of India.

In 1984, Balakrishna debuted in a hero role with Sahasame Jeevitham. Even though he acted in several films named as N. T. Rama Rao's son, later his hard work, discipline, talent and dedication made him stand in the industry and to win the hearts of audience. He then starred in the drama film Mangammagari Manavadu in 1984, alongside Bhanumathi and Suhasini, directed by Kodi Ramakrishna. The film was a blockbuster at the box office. In the same year, he acted in Kathanayakudu and in the biographical film Shrimad Virat Veerabrahmendra Swami Charitra. Both films did well at the box office. Again, his role as Siddhappa in Shrimad Virat Veerabrahmendra Swami Charitra was critically praised. This movie was directed by his father NTR. He also appeared in K. Viswanath's directorial Janani Janmabhoomi in 1984, which was a critical success. In the year 1985, he acted with Akkineni Nageswara Rao in the film Bharyabhartala Bandham, alongside Rajani, which was a moderate success. In the year 1986, he acted in movies such as Muddula Krishnaiah, Seetharama Kalyanam, Anasuyamma Gari Alludu and Deshoddharakudu, which gradually increased his potential at the box office.

In 1987, Balakrishna acted in a dual role in the film Apoorva Sahodarulu, directed by K. Raghavendra Rao, which was a box office success. In that year he had six successful films in a row. In the same year, he starred in President Gari Abbai, directed by Tatineni Rama Rao and Muvva Gopaludu, by Kodi Ramakrishna. Bhargava Ramudu, which is made from a novel, alongside Vijayashanti was a success at the box office. His other films like Inspector Pratap, Bharatamlo Bala Chandrudu, Tiragabadda Telugubidda, Raktabhishekam were also critically and commercially successful at the box office. In 1989, he paired with Vijayashanti in Muddula Mavayya directed by Kodi Ramakrishna. Bhale Donga alongside Vijayashanti and Sharada was also a success at the box office. In 1990, he acted in Nari Nari Naduma Murari, directed by A. Kodandarami Reddy, alongside Shobana and Nirosha. The film was a box office success. In the same year, he appeared in B. Gopal's Lorry Driver, opposite Vijayashanti. Talli Tandrulu with him alongside Vijayashanthiwas again a success at the box office.

In 1991, Balakrishna acted in a science fiction film Aditya 369, directed by Singeetam Srinivasa Rao. A sequel, tentatively titled Aditya 999, has been planned but not yet confirmed. This was the only science fiction film in Telugu cinema during that period of time. He then had two releases in 1992, Dharma Kshetram and Rowdy Inspector, directed by B. Gopal. In the year 1993, he had two releases on the same day, which are Nippu Ravva, alongside Shobana, Vijayashanti, directed by A. Kodandarami Reddy, Bangaru Bullodu, alongside Raveena Tandon and Ramya Krishna, directed by Ravi Raja Pinisetty. His next appearance was a folk role in Bhairava Dweepam in 1994, directed by Singeetam Srinivasa Rao. The film was a critical and commercial success and one of the milestones of his acting career. In Brahmarshi Viswamitra, directed by his father, he played as Satya Harischandra and Dushyanta. Between 1994 and 1999, he acted in movies such as Bobbili Simham, Vamshanikokkadu, Peddannayya and moderate successes such as Muddula Mogudu, Maato Pettukoku, Raana and Pavitra Prema. In the year 1999, he acted in B. Gopal's action film Samarasimha Reddy, opposite Simran and Anjala Zhaveri.

In 2000, Balakrishna acted in Goppinti Alludu, directed by E V V Satyanarayana with Simran. The film performed well at the box office. In 2001, he starred in the B. Gopal-directed faction film Narasimha Naidu, opposite Simran once again. The film broke several box office records and it completed 100 days in as many as 109 centres in the state and neighbouring states and had a silver Jubilee in a record 17 centres. The film became the highest-grossing Telugu film of all time until the record was broken by Chiranjeevi's Indra, which was also directed by B. Gopal. Balakrishna won his first Nandi Award for Best Actor for his performance. In the same year, he appeared in Bhalevadivi Basu with Shilpa Shetty and Anjala Zhaveri, which opened to average reviews. His 2002 and 2003 films include Seema Simham and Chennakeshava Reddy. The former received unfavourable reviews and was a box office flop, but the latter one was critically and financially successful. In 2004, he performed in a remake of the 2003 Tamil film Saamy, titled Lakshmi Narasimha, with Asin Thottumkal. The film and Balakrishna's performance won critical acclaim and was a financial success. During the period, he also announced plans to act and direct in the remake of Nartanasala, and a launch event was held in Hyderabad during March 2003. Produced by Pusapati Lakshmipati Raju, the film was announced to have an ensemble cast also featuring Soundarya, Srihari, Saikumar, Uday Kiran and Asin in lead roles. However, despite a grand launch, the film was later shelved following the sudden demise of Soundarya.

Balakrishna was involved in a shooting controversy. The incident took place on 3 June 2004 around 8:50 PM at Balakrishna's residence in Jubilee Hills, Hyderabad, when Balakrishna allegedly fired shots at Producer B. Suresh and his associate, Satyanarayana Chowdhary. Later, both the wounded were admitted into Apollo hospital. The circumstances under which the case was handled led to much controversy as purported by the Human Right Forum (HRF). The HRF questioned the authenticity of people who handled the case, and the circumstances under which Balakrishna was shielded from police by giving refuge in Care Hospital without any justifiable cause.

The years from 2005 to 2009 saw a lull in Balakrishna's career. Action-drama flicks such as Vijayendra Varma, Veerabhadra, Allari Pidugu, Okka Magadu and Maharadhi bombed at the box office. He paired with Sneha and Tabu in the mythological movie Panduranga (2008), directed by K. Raghavendra Rao. He played the dual roles of Krishna and Panduranga. Rediff described his performance as "Balakrishna does justice to both the roles of God and Ranga. He shines in the climax of the movie. It's quite a task to step into NTR's shoes, but his son has done pretty well, though one does miss NTR in the role of Krishna!". The film was an average success and his performance won him the Santosham Best Actor Award. In the year 2009, he starred in the family drama Mithrudu, alongside Priya Mani in a slightly different role – that of a dependable friend and confidante to the female lead. The film opened to average reviews.

In 2010, Balakrishna acted in Boyapati Srinu's film Simha, alongside Nayantara and Sneha Ullal. He played a dual role as father and son. The film opened to positive reviews, and went on to become the highest-grossing film of the year. A review in Rediff said about his performance: "Balakrishna has put in a restrained performance. Though his character is supposed to roar at times, he seems subdued most of the time. But he's given plenty to be pleased about as it is his show all the way." In 2011, he acted in a mythological film Sri Rama Rajyam, based on the epic Ramayana. He played triple role in the 2012 action drama Adhinayakudu, making him the first actor to play three different roles as a grandfather, father and grandson on the big screen. In 2014, he acted in Boyapati Srinu's film Legend, alongside Sonal Chauhan and Jagapati Babu. He played the title role in the biographical and historical film Gautamiputra Satakarni, his 100th film. The film is directed by Krish and is based on the life of the 2nd century ruler of the Satavahana Empire, Gautamiputra Satakarni.In 2018, he played Jai Simha movie, directed by K.S.Ravikumar.

Ever since the Telugu Desam Party formation, Balakrishna always campaigned for it in every election, but never entered the electoral battle. He went on a vacation to his father-in law Devarapalli Suryam's house. During the vacation, he went on a political campaign for TDP all over East Godavari district and made a victory for TDP. After coming to know about this, NTR said that the East Godavari victory is completely Balayya's victory. He contested in the 2014 Andhra Pradesh Legislative Assembly elections on behalf of TDP and won the Hindupur Assembly Constituency seat with a reasonable majority. Hindupur, in Anantapur district, has been a TDP stronghold since 1983. It was once represented by NTR himself and later for a term by his elder son Nandamuri Harikrishna and Balakrishna will be the third from the family to represent the State Assembly.

In his 100th film, he essayed Gautamiputra Satakarni, 2nd century ruler of the Satavahana Empire in the epic war film Gautamiputra Satakarni (2017). The film was subsequently dubbed into Hindi and Tamil languages. The film is screened at the first "Edinburgh Festival of Indian Films and Documentaries". Balakrishna has received three state Nandi Awards for Best Actor for his works in Narasimha Naidu (2001), Simha (2010), and Legend (2014). In 2014, he received the South Indian International Movie Award for best actor for his work in Legend. Balakrishna was the chief guest for the 43rd International Film Festival of India. Balakrishna is the Chairman of Basavatarakam Indo-American Cancer Hospital and Research. He is an elected member of the Andhra Pradesh Legislative Assembly for the Hindupur.