Nicholas "Nick" Stokes was born in Dallas, Texas to Judge Bill Stokes and Lawyer Jillian Stokes. He is the youngest of seven with at least one brother. As a child, he showed athletic and academic potential and played football. Overall, he had a happy childhood and had a close relationship with his parents. Nick's father calls him "Pancho" and Nick, in turn calls his father "Cisco", both characters from the television show, The Cisco Kid ("Grave Danger", season five). In Grave Danger, Grissom calls Nick, "Pancho" to calm him while rescuing him from a coffin that has been rigged with explosives. Nick's early life was not without pain; however, he was molested at age nine by a female babysitter (he revealed this information to Catherine Willows in "Overload"). Although it is never again directly addressed in the show, the manifestation of the trauma can be seen whenever the character has trouble investigating crimes against children, especially during episodes such as "Blood Drops", "Gum Drops", "Turn, Turn, Turn", "418/427", or "Unleashed".

Nick attended Texas A&E University, where he pledged at a fraternity ("Pledging Mr. Johnson", season one). After leaving college, he joined the police department and took a job with the Dallas crime lab and specialised in hair and fiber analysis. Feeling that he would not be able to match his parents' considerable academic achievement, Nick decided to leave Texas for Las Vegas, Nevada. In Las Vegas, Nick found that he could "be his own man" and in 1997, he joined the successful CSI team under the leadership of Gil Grissom.