Zack (SETH ROGEN) and Miri (ELIZABETH BANKS) are longtime friends and roommates who share an apartment in Detroit, but now don't have enough money to pay the rent or utilities. After a secretly taped video of Miri in her "granny panties" becomes a hit on the Internet, and Zack and Miri attend their high school reunion where they learn that former quarterback star Bobby Long (BRANDON ROUTH) is now a gay porn actor along with his boyfriend, Brandon (JUSTIN LONG), the lifelong friends come up with an unlikely idea.
And that's to make a homemade porn film to earn money. With Zack's coffee shop coworker, Delaney (CRAIG ROBINSON), serving as their producer, and former high school AV cameraman, Deacon (JEFF ANDERSON), as their cinematographer, Zack will work as the director and Miri will be the star, although the plans are for her only to have sex with Zack on camera. For the rest, they hold auditions and hire the likes of Lester (JASON MEWES), Bubbles (TRACI LORDS), Stacey (KATIE MORGAN) and Barry (RICKY MABE) to fill out the cast.
From that point on, Zack and Miri must contend with the aftereffects of them sleeping together for the first time, all as they try to guide their porno film through to completion.