"The Pick of Destiny" is presented as a documentary-style film, chronicling the early days of Tenacious D. The story begins with Jack Black's character, JB, meeting Kyle Gass's character, KG, at a Hollywood open mic night. The two musicians quickly form a bond over their shared passion for rock music and decide to form a band. The film follows their journey as they struggle to make it big, overcome creative differences, and battle rival musicians.