Usually content just to hang out near a Jersey convenience store, deal drugs and discuss any variety of issues, verbose and vulgar stoner, Jay (JASON MEWES), and his taciturn friend, Silent Bob (KEVIN SMITH), have a new beef. Upon visiting Brodie Bruce (JASON LEE), a local comic book maven, the two discover that their friends, Banky Edwards (also JASON LEE) and comic book artist Holden (BEN AFFLECK), have sold them out by selling the rights for a movie starring their comic book alter egos, Bluntman & Chronic.
After then learning that they're also being bad-mouthed on the Internet about supposedly selling out to Miramax who will produce the film, Jay and Silent Bob then decide they must stop the movie, lest their reputations be tarnished forever. Accordingly, they set out for Hollywood and in doing so, run into various interesting characters along the way.
Among them is a hitchhiker (GEORGE CARLIN) who shows the two a unique way to get rides, as well as a quartet of attractive young women -- Sissy (ELIZA DUSHKU), Chrissy (ALI LARTER), Missy (JENNIFER SCHWALBACH) and Justice (SHANNON ELIZABETH) - who want to use Jay and Silent Bob as their patsies for a diamond heist after their after fall guy, Brent (SEANN WILLIAM SCOTT), is jettisoned from both their van and plan.
That fiasco inevitably teams the two with an orangutan and sets them in the sights of Federal Wildlife Marshal Willenholly (WILL FERRELL) who will track them across the country to bring them to justice, especially after they're mistaken for being militant animal rights activists.
As the two eventually arrive in Hollywood and encounter both the famous - including Ben Affleck and Matt Damon - and others such as a security guard (DIEDRICH BADER) who joins in the pursuit of them, Jay and Silent Bob do what they can to find and stop the movie -- that's being directed by Chaka (CHRIS ROCK), an angry African-American filmmaker - before their lives are ruined forever.