[2] Born in Connecticut and raised in Atlantic Highlands, New Jersey, Anderson attended Henry Hudson Regional High School, with his friend, aspiring writer Kevin Smith; they graduated in 1988.

As a joke, Anderson auditioned for the role of "Jay,"[citation needed] and based on this audition, Smith later offered Anderson a lead role as video store employee Randal Graves, a foul-mouthed apathetic slacker, who patronized, angered, and mocked his customers while avoiding any real work opportunities.

Anderson received a nomination for Best Male Performance at the Chicago Film Festival for his role in Love 101, and has been seen in Peter Bergstrom's Something Cool.

Anderson was initially reluctant to reprise his role as Randal, but changed his mind after reading Kevin Smith's screenplay for Clerks II, and in 2006 appeared in the sequel.

[6][7] On October 1, 2019, Smith announced on Instagram that Clerks III was happening and that Anderson agreed to reprise his role as Randal.