Hirani was born on 20 November 1962 in Nagpur to a Sindhi family. His ancestors originally belong to Mehrabpur, a city now in the Naushahro Firoz District, Sindh, of Pakistan. His father Suresh Hirani ran a typing institute in Nagpur. Rajkumar Hirani studied at St. Francis De’Sales High School, Nagpur, Maharashtra. He did his graduation in commerce. His parents wanted him to be a chartered accountant, but he was more keen on theatre and film.

In 2003, Hirani made his directorial debut with the comedy film Munna Bhai M.B.B.S. starring Sanjay Dutt, Arshad Warsi, Boman Irani, Gracy Singh, Jimmy Sheirgill, and Sunil Dutt. It was about the titular protagonist (played by Sanjay Dutt), a goon going to a medical school who is helped by his sidekick (Circuit, played by Warsi). The film received a positive response from critics. Hirani’s direction was praised, and the film emerged as a major commercial success with a worldwide total of ₹1 billion (US$14 million). Munna Bhai M.B.B.S. won the National Film Award for Best Popular Film Providing Wholesome Entertainment and the Filmfare Critics Award for Best Film, and earned Hirani his first Filmfare Award for Best Screenplay and a nomination for the Filmfare Award for Best Director. The film was the first film of the franchise Munna Bhai.

In 2006, Hirani directed the second installment of the Munna Bhai franchise, titled Lage Raho Munna Bhai, which retained some of the original cast, including Sanjay Dutt, Warsi, and Boman Irani, and added Vidya Balan as the female lead replacing Gracy Singh. The feature proved to be Hirani’s highest-grossing release to that point, earning over ₹1.93 billion (US$27 million) worldwide, thus attaining a blockbuster status and becoming the third highest-grossing film of that year. Just like the previous film, it won the National Film Award for Best Popular Film, and earned Hirani a second Critics Award for Best Film award, a first Best Story award, a first Best Dialogue award, and a second Best Director nomination at Filmfare.

In 2014, Hirani directed PK. PK was released on 19 December 2014. It received mixed reviews, with praise for the performances, particularly by Khan. The film received eight nominations at the 60th Filmfare Awards, winning two. PK was the first Indian film to gross more than ₹7 billion and US$100 million worldwide. At the time, it emerged as the highest-grossing Indian film of all time, and ranks as the 70th highest-grossing film of 2014 worldwide. The film’s final worldwide gross was ₹854 crore (US$140 million).

He also directed Sanju (2018). The film follows the life of Bollywood actor Sanjay Dutt, his addiction with drugs, arrest for alleged association with the 1993 Bombay bombings, relationship with his father, comeback in the industry, the eventual drop of charges from bombay blasts, and release after completing his jail term. Upon release, it generally received positive reviews from critics and was praised for Kapoor and Kaushal’s performance; some criticised its image-cleansing of its protagonist. It registered the highest opening for any film released in India in 2018, and on its third day, it had the highest single day collection ever for a Hindi film in India. With a worldwide gross of ₹586.85 crore (US$82 million), Sanju ranks as the highest grossing Bollywood film of 2018, the second highest-earning Hindi film in India of all time, and one of the highest-grossing Indian films. Sanju earned seven nominations at the 64th Filmfare Awards, including Best Film and Best Director for Hirani. It won two; Best Actor for Kapoor and Best Supporting Actor for Kaushal.