Two underachieving pot smokers, Silas (Method Man) and Jamal (Redman) are visited by the ghost of their recent deceased friend Ivory (Chuck Davis). Ivory was cremated and Silas's used his ashes as fertilizer for a new batch of marijuana. While both are sitting in the parking lot before taking their "THC" (Testing for Higher Credentials, a parody of the SAT in allusion to Tetrahydrocannabinol) exams for college, neither is able to smoke his individual marijuana stash without the help of the other.
They soon discover that smoking Silas's new batch summons the ghost of the recently deceased Ivory, visible to just the two of them. Ivory tells them the test answers as they take the test and they both score perfect scores. Several dubious colleges offer the pair scholarships, but none of them are appealing. Eventually, Chancellor Huntley (Fred Willard) suggests the two apply to Harvard University.
Once there, they meet Bart (Chris Elwood), captain of the rowing team, his girlfriend Lauren (Lark Voorhies), I Need Money (Al Shearer), and their roommates Jeffrey (Justin Urich) & Tuan (Trieu Tran). Once they are settled in, they visit Dean Carl Cain (Obba Babatundé) who tells them that per the terms of their scholarship, they must maintain a minimum grade point average of 2.0 in order to remain at Harvard, or else face expulsion.
Jamal joins the rowing team hoping to outrank Bart. Silas enrolls in the botany class to develop his "herbal" skills. They both enroll in black history together, although there are two other classes in which they have enrolled alone. Throughout the first half of the school year, they pass every test with the help of Ivory. Silas continues to woo and study with Lauren, while Jamal dates the U.S. vice president's daughter Jamie (Essence Atkins).
Also during the first half of the semester, they pull pranks and steal, which angers Bart, Jeffrey (who is pledging for a Final Club), and Dean Cain. Things go downhill after Silas and Jamal's raucous Halloween party. At the party, Gerald (T. J. Thyne), the volunteer officer whose bicycle was stolen and crushed by I Need Money, steals and smokes the Ivory plant, leaving the pair without access to Ivory.
Silas begins working on a truth serum for his Botany class, using plant extracts. Silas concludes that, if his experiment works, he will earn an A in Botany, and a guarantee of a next semester. Hhis experiment fails numerous times. Before midterm examinations, Jamal suggests they go to a graveyard, dig up a "smart dead guy", and smoke his remains; Silas suggests simply that they study hard for a few hours a day while high. They try Silas's plan, but it does not pan out, as they end up failing almost all of their midterm exams.
Desperate to stay in Harvard, they try Jamal's plan, but it proves fruitless, as well. Meanwhile, Gerald, who has morphed into a complete stoner, sees Ivory during one of his binges, and, at Ivory's behest, returns the remnants of the Ivory plant to Jamal and Silas. Due to Gerald's abuse of the plant very little remains and Jamal and Silas continue to fail their classes, which pleases Dean Cain.
With the last final exam approaching, Jamal and Silas resign themselves to give up. However, Jeffrey reminds Silas of his guarantee of another semester if he can successfully fix his truth serum experiment. Silas ultimately does, having found a solution in which the last of Ivory's leaves could be used to counteract nausea.
Nonetheless, because of their low grades, Jamal and Silas do not receive an invitation to the Harvard Alumni party. Dean Cain, clearly thrilled with this result, tells Bart he does not have to worry about the pair showing up or staying in Harvard. However, that changes when Jamie invites them both as her dates, as her father is an alumnus. At the party, Silas makes things a bit more interesting by testing out his truth serum experiment, which proves successful.
At Lauren's presentation at the alumni party of Benjamin Franklin's artifacts, she shocks everyone with her discovery: the artifacts turn out to be a bong. Dean Cain is outraged by this finding, but the Chancellor decides that he has had it with the Dean and fires him. Jamal and Silas are proud that the serum worked, a celebration that was almost short-lived, as Dean Cain returns and unsuccessfully attempts to kill them both. He is eventually apprehended by Secret Service. At the end, Jamal and Silas are able to stay, Jamal and Jamie get approval of Jamie's father to date, and Lauren leaves Bart for Silas because Bart "can't satisfy her".
How High received generally negative reviews from critics, it received an approval rating of 27% rating from Rotten Tomatoes based on 52 reviews, with the sites consensus stating: "How High is a sloppily constructed stoner movie filled with lame, vulgar jokes."
Mike Clark of USA Today said the film "has neither the redeeming social value of a cockfight nor enough material to sustain its 91 minutes."
Entertainment Weekly rated it third in their "Best Stoner Movie" top ten list. The movie also won the Stony Award for Best Stoner Movie in 2002.
In October 2008, Redman revealed that a script for the sequel was in the middle of being written, stating that "we wanna represent all the smokers", believing that since How High, no one has done justice on a stoner film. In April 2009, it was reported that Redman blames Universal Pictures for the film's delay, stating: "They're not opening that money door for us to shoot it. We promoted the shit out of that movie. We got the whole world waiting for a How High 2."
In November 2010, Redman further stated, "Blackout! 3 is coming, Muddy Waters 2 is coming and How High 2 is coming. But remember, Universal owns the rights to How High. They own the names, they own the characters, they own the whole thing. If Red and Meth do a movie, we can't call it How High. Only person that can get us out of that is Keenen Ivory Wayans."
In December 2010, Redman confirmed that Universal Pictures is indeed holding the rights to How High, so the chances of How High 2 coming out are slim. In April 2013, Method Man told TMZ that the script was currently being written by Dustin Lee Abraham, who wrote the first one, but it all would depend on Universal if the film will take place.
In November 2015, Redman stated that How High 2 will be released in 2017.
In 2017, there was a written script, with the sequel's title "Too High", confirmed by Matt "M-80" Markoff. Redman stated that the script is being "rewritten" because he did not like the script. He expects production to begin late 2017, early 2018.