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.

In 2002, Anderson wrote, directed, and starred in Now You Know. The writing process lasted only three months. 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 also started his own production company in Hollywood. In 2006, Anderson reprised his role as Randal in Clerks II.

In 2008, Anderson appeared in Kevin Smith's romantic comedy Zack and Miri Make a Porno as Deacon, the cameraman and film Editor for the porno made by leading stars Seth Rogen and Elizabeth Banks.

On September 14, 2010, Anderson made his first appearance on Smith's SModcast filling in for Scott Mosier on SModcast #134. In his podcast, Anderson stated he had moved out of Los Angeles and into a "retirement community in the mountains" where he is "the youngest person there by 20 years." He also said he remarried in 2009, to an Actress named Barbara Jacques he met while house sitting for Kevin Smith.

In April 2017, it was confirmed that production on the proposed sequel Clerks III had ceased, as Anderson was not interested in appearing in the Kevin Smith directed film. Although an $8 million budget had been obtained, locations were being scouted in Philadelphia and a crew was being assembled, with less than 2 months until production was to start, Anderson decided he would not be involved; the reasons have not been made public. Smith said he would not recast the role and production on the film was halted indefinitely.