He was born on 7 July 1963 in Delhi. His father worked for the Claridges hotel in New Delhi. He was a part of the selection camp as a Swimmer in the 1982 Asian Games held at New Delhi but was not selected in the final round. He studied at Air Force Bal Bharati School in Delhi.

Mehra started off by selling vacuum cleaners for Eureka Forbes. In 1986, he established Flicks Motion Picture Company Private Limited, starting his career as an advertisement film maker. He directed scores of television commercials for Indian and international clients, including Coke, Pepsi, Toyota, American Express and BPL. He has also directed music videos such as Aby Baby starring Amitabh Bachchan.

In 1992, Rakeysh married P.S. Bharathi. The couple have a daughter, Bhairavi, and a son named Vedant.

Mehra then gradually transited from being an ad-film maker to a feature film maker. In June 2001, his company released its first full-length feature film titled Aks, starring Amitabh Bachchan. Directed by Mehra, Aks was critically acclaimed for Bachchan's performance, but did not do well at the box office.

Mehra's second film, which he produced and directed, was Rang De Basanti. Released in 2006, it starred Aamir Khan and Soha Ali Khan. The film was a huge hit in India and did very well overseas. Mehra received much acclaim for the film, winning Best Director awards at the 2006 Filmfare Award and National Film Award as well as a BAFTA Award nomination for Best Foreign Language Film. The film was also officially chosen as India's entry to the Oscars.

Mehra's third release, again produced and directed by him, was Delhi-6 (2009), starring Abhishek Bachchan, Sonam Kapoor, Om Puri, Waheeda Rehman, and Atul Kulkarni. The film got lukewarm critical response and its performance at the box office was also very lukewarm.

Mehra then produced (but did not direct) the film Teen They Bhai (2011). Directed by debutant Mrighdeep Lamba, it was a story about three brothers who keep fighting amongst themselves. The film neither won any critical acclaim nor did well at the box-office, and was an all-round disaster.

Mehra's next directorial venture was the biopic Bhaag Milkha Bhaag (2013) starring Farhan Akhtar as Milkha Singh, the legendary Indian sprinter. The film, which was produced by a consortium of several producers, was a major commercial and critical success, the second of Mehra's career.

Mehra's latest film is Mirzya (2016), a contemporary retelling of the tragic love story of Mirza & Sahiba. Set in Rajasthan, the film marked the debut of two newcomers, namely Harshvardhan Kapoor (son of actor Anil Kapoor) as Mirzya, and Saiyami Kher, granddaughter of veteran Actress Usha Kiran, as Sahiba. Gulzar emerged from a long hiatus to write the screenplay of the film, and Shankar–Ehsaan–Loy were entrusted with the music direction. Released on 7 October 2016, Mirzya proved to be an unmitigated disaster at the box office. Made on a budget of Rs.35 crore (350 million), its total collections over a two-week period amounted to less than Rs.10 crore (100 million). The film, which had been in the planning since at least 2009, and was made over a three-year period, ran for only one week in most theatres, losing nearly all its screens at the end of that period. Nor did it receive positive critical reviews: nearly all reviewers stated that the film failed to touch or involve the viewer in any way, consisting mainly of a series of picture postcard visuals and soaring, rather pretentious music.

Rakeysh Omprakash Mehra Pictures is currently producing two films. Fanne Khan, which is being directed by a debutant Director Atul Manjrekar. Fanne Khan is starring Aishwarya Rai Anil Kapoor Rajkummar Rao and is set to release in 2018. Mere Pyaarey Prime Minister is the other film which has been directed by Rakeysh Omprakash Mehra himself and it is written by Manoj Mairta. It is about an 8 year old boy wanting to build a toilet for his mother.