Nagesh Kukunoor was born to Kusuma and Sudarshan in Hyderabad. As a child he loved watching Telugu, Hindi, and English films in the theatres of his neighbourhood, Narayanguda. Nagesh Kukunoor attended Osmania University in Hyderabad, India and received his Bachelor's degree in Chemical Engineering. He moved to Atlanta, Georgia in the United States in 1988, and completed his Master's degree in Environmental Engineering at Georgia Institute of Technology. After graduating from Georgia Tech, he went to work as an Environmental Consultant at Trinity Consultants in Texas, then in Atlanta, during which he attended workshops in film. He studied Acting & direction at the Warehouse Actor's Theater in Atlanta.
He invested the money he made from his engineering career in USA in producing the 1998 movie Hyderabad Blues. It is based on a script that he wrote in Atlanta dealing with Indians returning home from the United States of America. He directed and acted in the movie. It was a budget of Rs. 1.7 million (roughly equivalent to US$40,000) and shot in 17 days. It was perceived by Sanjay Arora, an independent film maker, to be realistic and among one of the first movies to use Hyderabadi Urdu correctly. It became the most successful independent film in India. The film was featured at Peachtree International Film Festival in Atlanta and Rhode Island International Film Festival.
3 Deewarein (2003) was premiered at the Kolkata Film Festival. In contrast to his earlier work, it had a budget of ₹21 million (US$320,000) and featured established actors including Naseeruddin Shah, Juhi Chawla and Jackie Shroff.
In 2006, Nagesh KuKunoor wrote and directed Dor, a drama film featuring Ayesha Takia, Gul Panag and Shreyas Talpade as the lead actors. Nagesh also acted in the film, playing the role of businessman Chopra. The film is about two women who come from different backgrounds and how fate brings them together. Meera (Ayesha Takia), a young woman who becomes a widow shortly after marriage, is trapped by tradition. Zeenat (Gul Panag), on the other hand, faces the daunting task of saving the life of her husband, who is on trial for murder. A bahuroopiya (Shreyas Talpade) helps her reach Meera, who holds the "string" to Zeenat's hope. The companionship that develops between Meera and Zeenat results in redemption for both. The film was well received by both, the critics and film buffs.
8x10 Tasveer (2009), features Akshay Kumar in the lead role and Ayesha Takia as the female lead it is a thriller with a touch of Hollywood style cinematography, but fared poorly at the box office. It is considered to be Nagesh's most self-reflective work to date. "I like to cast characters who are close to me. And this one gets as close to me as possible. I was once an environmental consultant. Akshay plays the part of an environment protection officer," Kukunoor said in an April 2009 interview.
In 2015, at the 65th Berlin International Film Festival, his feature Dhanak won The Grand Prix of the Generation Kplus International Jury for the best feature-length film, plus it also a Special Mention by Children's Jury in Generation Kplus Section .