Smith originally intended this to be the last film to utilize his View Askewniverse, or feature Jay and Silent Bob. Five years later Smith changed his mind and decided to close out the series with Clerks II, resurrecting Jay and Silent Bob in supporting roles. In the end credits for that film it states the two might return someday.
On the way, they befriend an animal liberation group, consisting of four women and one man, Brent (Seann William Scott), they had picked up for the cause. It is revealed that the organization is a front; Brent is a patsy, intended as a diversion by freeing an animal from a testing laboratory while the girls rob a diamond depository nearby. Jay tricks Brent and throws him out of the van in order to get closer to Justice (Shannon Elizabeth), the most compassionate of the women and the one with whom he finds himself smitten. Justice then reluctantly accepts Jay and Bob as the new patsies.
While the girls are robbing the diamond depository they accidentally set off the alarm, prompting them to break the glass and steal the diamonds. While this is going on Jay and Silent Bob free the animals (taking an orangutan, Suzanne, with them and letting the others loose). They escape outside to see the police arriving and the van exploding, which they believe has killed the girls.
Jay then takes the orangutan with him as a memorial to Justice. Quickly afterwards Federal Wildlife Marshall Willenholly (Will Ferrell) shows up at the scene. Blinded to the diamond heist, he claims to have jurisdiction because "somebody let out all these animals". He learns that all the animals have been recovered except for the orangutan.
When the officers later have the trio cornered inside a diner and threaten to open fire, Jay and Silent Bob dress the orangutan as a child and walk out, claiming that they want to get their "son" out of the danger zone. Marshal Willenholly, thinking about the political repercussions of an alternate-lifestyle family going back to their liberal-minded city with tales of prejudice and bigotry from Utah, decides to let them leave, but he quickly realizes his mistake and resumes the chase. When they jump into a sewer system, only Willenholly himself follows them, and he is soon tricked into jumping off of the dam.
Having escaped the law, Jay and Silent Bob once again return to their quest to reach Hollywood only to have Suzanne taken by a Hollywood animal acting agency car. Now on a quest to get their ape back and to clear their names, the two once again embark to Hollywood.
On their arrival in Hollywood, the two find themselves in the background of a news cast (ironically about their kidnapping Suzanne) that Justice is watching. While Justice takes the diamonds and goes to Hollywood to set things right, Marshal Willenholly learns of their mission to reach Hollywood and leaves to find them.
After a long chase with Studio Security and reclaiming Suzanne, Jay and Silent Bob end up in Jason Biggs and James Van Der Beek's dressing room, where they quickly realize that these are the actors that will play the roles of Bluntman and Chronic. (Ironically, Jay asks Jason Biggs "did you get the third base from that Russian chick like in the movie" referring to the character of Nadia in American Pie portrayed by Shannon Elizabeth.) Suzanne beats both of them up effortlessly and Jay and Silent Bob assume the roles of their characters, Bluntman and Chronic. Being forced into their costumes and thrown on stage, they must engage in a duel with Cock-Knocker (Mark Hamill), eventually taking a break from the scene when Willenholly interrupts to capture Jay and Silent Bob. During this final scene, Justice and her former jewel thief team arrive, and a climactic final battle ensues, after which Jay and Silent Bob get their royalties to the film, and Justice turns herself and her former team in to Willenholly in exchange for a shorter sentence and letting Jay and Silent Bob go.
The film ends with Jay and Silent Bob spending their royalty money on finding everybody who expressed negative opinions about the movie and characters, ranging from kids to clergy, and traveling to their town to beat them up, followed by Jay and Silent Bob with most of the cast enjoying a performance from Morris Day and The Time.
Music from the Dimension Motion Picture Jay and Silent Bob Strike Back, the soundtrack to the film, was released on August 14, 2001 by Universal Records. It alternates film dialogue with songs of various genres that appear in the film. It features the 2001 Afroman hit, "Because I Got High", whose music video featured the characters Jay and Silent Bob.
The film made $30,085,147 in the domestic market, and an additional $3,703,014 overseas, for a total of $33,788,161 gross in theaters.