James Gunn was born and raised in St. Louis, Missouri, to Leota and James Francis Gunn. He is from a large Catholic family, with Irish and Czech ancestry. His father and his uncles were all lawyers. He has been writing and performing as long as he can remember. He began making 8mm films at the age of twelve.
He began his career as a screenwriter in the mid-1990s, starting at Troma Entertainment with Tromeo and Juliet (1997). He then began working as a director, starting with the horror-comedy film Slither (2006), and moving to the superhero genre with Super (2010), Guardians of the Galaxy (2014), Guardians of the Galaxy Vol. 2 (2017), The Suicide Squad (2021), and Guardians of the Galaxy Vol. 3 (2023). In 2022, Warner Bros. Discovery hired Gunn to become co-chairman and co-CEO of DC Studios.