Neil Nitin Mukesh was born in Mumbai to Bollywood playback singer Nitin Mukesh and Nishi Mukesh. He was named by Lata Mangeshkar after astronaut Neil Armstrong as his father was a big fan of Neil Armstrong. After schooling at Greenlawns High School in Mumbai, he graduated from HR College with a Bachelor's degree in Communications. He did a 4-month workshop with Kishore Namit Kapoor and also at Anupam Kher's institute during his college vacation. He also assisted Aditya Chopra in his film Mujhse Dosti Karoge while still in college.
As a child, Mukesh appeared in Vijay (1988) and Jaisi Karni Waisi Bharni (1989). He received several offers as a lead actor before his acting debut as an adult, but as he did not want to debut with a love story, he chose to wait for the right role. It was then that Sriram Raghavan offered him Johnny Gaddaar Although the movie did not do well at the box-office, his acting was appreciated.
His next films were Aa Dekhen Zara, New York and Madhur Bhandarkar's Jail. He also appeared in Yash Raj's Lafangey Parindey.
His upcoming films include, Italian Job and 7 Khoon Maaf. The last one being directed by Vishal Bharadwaj, stars Priyanka Chopra alongside John Abraham, Irrfan Khan, Naseeruddin Shah and Annu Kapoor. Priyanka plays the role of a woman who has seven husbands of which the youngest one is being played by Mukesh.