James Lafferty was born on July 25, 1985 in Hemet, California. His acting career began at age six. At age 10, he earned his first speaking role. He was encouraged by his mother to act as a hobby, who also urged his brother to act at the same time. He attended Hemet High School, where he played basketball for the Varsity team, earning him an MVP award and an All-League award. In 2003, he graduated from high school and enrolled at California State University, Long Beach.

In 2001, Lafferty landed a role on the short-lived television series Emeril. He portrayed Emeril's son. Lafferty also guest starred on Once and Again, Get Real, and Boston Public. This led to his role in the movie A Season on the Brink. The film was a basketball movie about the 1985-1986 season of Indiana University's men's basketball team. It was based on the book by John Feinstein. Lafferty portrayed the character of Steve Alford. In 2003, fresh out of high school, he was cast as Nathan Scott on the television series One Tree Hill.

Lafferty currently resides in Wilmington, North Carolina. He is a supporting partner of the professional basketball team, the Wilmington Sea Dawgs, part of the Premier Basketball League. He is currently working on a docudrama about this minor league basketball team in Wilmington, North Carolina.

Lafferty used to be affectionately called "Baby James" by his co-stars of One Tree Hill, because he is the youngest member of the main cast, having been only 17 when they shot the pilot. However, he has not been called by this nickname publicly since the first season.

In December 2007, it was reported by Rush & Molloy in the New York Daily News that Lafferty has "now hooked up with" co-star Sophia Bush the report also mentioned that a rep for the actress has denied there is any romance. Recently, photos surfaced of Lafferty and Bush at LAX and LAX Baggage Claim together, which fueled rumors of a possible romance.

An adamant basketball fan and athlete, Lafferty plays the sport in his spare time. He played for the New Orleans Hornets at the 2008 NBA All-Star Game alongside Ne-yo Terrell Owens, Taylor Hicks and Master P. Their team won 51-50 with Owens being named Game MVP.