In 1977 Los Angeles, Holland March is a private eye hired by Mrs. Glenn to find her niece, porn star Misty Mountains, who she claims to have seen after her death. March's investigation leads him to Amelia Kuttner. A fearful Amelia pays Jackson Healy, a violent enforcer, to scare March away. After visiting March at his home and breaking his arm, he accepts a Yoo-Hoo from March's daughter, Holly, as he leaves. When Healy returns home (with a case of Yoo-Hoo), he is interrogated by two thugs, "Blueface" — so named after he sets off a dye pack while searching Healy's apartment — and Older Guy, about Amelia. Believing Amelia is in danger, Healy wards them off and teams up with a reluctant March to find her.
The duo visit Amelia's anti-pollution protest group and meet Chet, who brings them to the burnt-down house of Amelia's boyfriend Dean, who died in the fire. They learn that Amelia and Dean were working with Misty on an "experimental film" combining pornography and investigative journalism.
The two infiltrate a party to search for the film's financier Sid Shattuck. At the party, Healy discovers the film is missing, while March stumbles upon Shattuck's dead body and crosses paths with Amelia. March's daughter Holly, having snuck along to the party, stops Blueface from killing Amelia. Blueface is struck in a hit-and-run and Amelia flees. Healy subdues Older Guy and finds Blueface dying. Blueface tells Healy that his boss has dispatched a hit man named John Boy to kill all witnesses. Healy discreetly kills Blueface by strangling him. The police arrive at the scene.
March and Healy are met by Amelia's mother Judith Kuttner, a high-ranking official in the Justice Department. Judith claims Amelia is delusional and hires them to find her, for which March demands 5,000 USD in payment. March and Healy go to an airport hotel where Amelia is meeting with distributors for the film. However, John Boy has arrived ahead of them and is slaughtering the distributors. The duo hastily retreat, only for Amelia to land on their car and accidentally knock herself unconscious.
They take her to March's house, where she accuses her mother of colluding with car makers to suppress the catalytic converter, which regulates exhaust emissions. Amelia created the film to expose their collusion and believes her mother has been killing everyone connected to the film. A disbelieving March calls Tally, Judith's assistant, and tells her Amelia has been found. Tally tells him the family's doctor will arrive to check on Amelia. At the same time, she tasks them with delivering a briefcase of money to Judith.
March accidentally crashes his car during the delivery, causing the briefcase to fly open, spilling out shredded paper; the delivery was really a diversion to draw them away from Amelia. John Boy arrives at March's house disguised as the family doctor, attacks Holly and her friend Jessica, and engages in a shootout with the returning March and Healy. As John Boy evades the police, Amelia flees the house and unwittingly flags down his car only to be shot and killed. The police question and release March and Healy, who have no evidence that Judith is behind the murders. March realizes that Mrs. Glenn saw Misty in a film projected against a wall. At Misty's house, they discover a film projector, with no film. They realize that Chet is the projectionist for the Los Angeles Auto Show and will try to screen the film at the event.
At the auto show, Tally intercepts Healy and March at gunpoint. Holly distracts Tally, who is knocked unconscious. Amelia's film, which Chet spliced into the auto show presentation, implicates the auto executives. On the rooftop, March struggles with Older Guy, who falls to his death as March lands in the pool after both fall from the roof. Holly stops Tally from reaching the film. Healy overpowers John Boy, but spares his life at Holly's behest and March secures the film from thugs sent by the auto executives. Judith is arrested, but insists that it was Detroit who wanted Amelia dead; she hired March and Healy to keep Amelia safe. Judith remarks that while she will go to prison, Detroit has still gotten away with trying to suppress the catalytic converter. At a bar on Christmas Eve, March shows Healy an advertisement for their new detective agency called "The Nice Guys".
