The setting is the city of Los Angeles, California in the year 1977.
A young boy, Bobby (Ty Simpkins) sneaks into his father's room and takes out a porno magazine from under his bed. Bobby checks out the centerfold, adult film star Misty Mountains (Murielle Telio). In the distance, a car rolls down a hill. The car then crashes through Bobby's house and out into a ditch. He runs outside to check it out. A young woman is sprawled out nude a few feet from the car. It's Misty. She sees Bobby and asks "How do ya like my car, big boy?" before she dies. Bobby takes his shirt off and covers Misty.
In the next scene, we meet enforcer Jackson Healy (Russell Crowe). He follows a man that has been seeing a 13-year-old girl and smoking pot with her. When the girl leaves the man's house, Healy knocks on the door and then slugs the man square in the face, then tells her to stay away from young girls.
Private Investigator Holland March (Ryan Gosling) is sitting in his bathtub full of water wearing a nice suit. He has "You will never be happy" written on his hand. He lives with his daughter Holly (Angourie Rice) after his wife passed away, and he has become an alcoholic. As a PI, March doesn't get the best jobs. He meets with an old woman who claims her husband is missing. March notices an urn over the fireplace with her husband's name on it (and his ashes inside it).
Healy meets a teenage girl named Amelia (Margaret Qualley). She gives him March's name and address on a pink note shaped like a cow. March is looking for Amelia because he was hired by a woman, Mrs. Glenn (Lois Smith), to find her niece, Misty. Mrs. Glenn claims to have seen Misty appearing at her window in a pinstripe jacket, despite March insisting that Misty is dead and that she really saw Amelia. March goes to a bar to ask around, but the bartender threatens him with a bat for not leaving. Later, March tries to break in through the backdoor, but he cuts his wrist badly and has to go to the hospital.
Healy goes to March's house and punches him in the face, then kicks him in the stomach. He tells March to stay away from Amelia. March goes for the cookie jar to get his gun, but Healy knocks it out of his hand and then breaks March's arm. On his way out, Healy meets Holly, claiming to be a friend of her dad. She gives him a bottle of chocolate Yoohoo.
Healy goes home and is attacked by two men, known only as "Older Guy" (Keith David) and "Blueface" (Beau Knapp). They are looking for Amelia as well. Blueface goes into the next room to look for some money that Healy was holding, only to get sprayed with blue dye (hence his name). Blueface shoots at Healy, but Healy escapes.
March is at a bowling alley with Holly and her friends for her birthday. Healy approaches him in the bathroom, but March is prepared with a gun. The two sit down to talk about Amelia. March explains his case to Healy and demands a nice cut of the pay if he's gonna let Healy work with him on this. Healy agrees.
Healy and March walk by the Department of Justice building and come across a group of protesters lying on the ground, claiming the air is polluted and killing them. The group was organized by Amelia, so March figures she would be there. Some of the protesters tell them that Amelia isn't there. March offers $20 to anyone who will help. A guy named Chet (Jack Kilmer) joins the two and takes them to the home of Amelia's boyfriend Dean. The house has been burnt down. A kid on a bike passes by and asks for $20 to give up information. He knows Amelia and says she was with a guy named "Sid Hatrack", and that they made an "experimental" movie together.
Healy and March drive by a billboard for a "Pinocchio" porno produced film by Sid Shadduck, the man that the kid mentioned. After getting his information, the two attend a party at Shadduck's with many porn stars in attendance. Holly tags along by stowing away in the trunk of March's car, but he sends her away in a cab. Healy and March go around looking for information on Amelia. Healy goes into a room with costumes and a film reel titled, "How do ya like my car, big boy?", along with a pinstripe jacket and a pink cow note with what looks like flight information. He finds Holly in a room with a porn star watching a porno. Meanwhile, March is really drunk and ends up stumbling down a hill where he loses his gun. He sees Amelia, and she sees him, but he's too drunk to notice it's her. He finds his gun and then tries to light a cigarette, and his lighter illuminates a dead man's body. March calls Healy over to check it out. Healy goes through the man's pockets and learns that this is Sid Shadduck. March says they need to get rid of the body in case Amelia tried to place him since he said he lost his gun out loud. The two dump Shadduck's body over a fence, where it crashes onto the table of a wedding reception, horrifying everyone.
Holly comes across another porn star that knows she's been asking about Amelia. She guides Holly to a limo where she gets trapped with Blueface. Simultaneously, Healy runs into Older Guy. The two fight as Older Guy tries to shoot Healy, but Healy gets the upper hand and lets him live after he beats him down. Blueface sees Amelia and opens the door to shoot at her, but Holly slams the door on his hand and yells at Amelia to run before making her own getaway. March shows up after they left, but the valet tells him that Holly was in the black car. March steals a car and chases after it.
Holly and Amelia both end up cornered in the middle of the road by Blueface. A van drives by and slams into Blueface. Amelia is ready to run but Holly wants to help Blueface as he is suffering. Amelia flees and Holly goes to get help. Healy shows up and finds Blueface. He threatens Healy with the fact that someone called "John Boy" is going to find him and kill him. Healy then chokes Blueface to death before Holly returns. March drives by and runs to his daughter. Not long after, the paramedics show up, along with a detective named Tally (Yaya Dacosta). A limo pulls up to Healy and March. It is Judith Kuttner (Kim Basinger), head of the Department of Justice. She says she's Amelia's mother.
Healy and March sit with Kuttner in her office. She explains that the Vegas mob is trying to push their porn industry to L.A., and Amelia is involved because of the "experimental" movie she did with Shadduck, which Kuttner thinks is the result of her lashing out. Dean was murdered in his home as it burnt down so that the movie would be destroyed. She hires Healy and March to find her.
Back at March's house, March is lying on the diving board above his pool. Healy comes by, and March asks him why Tally earlier referred to him as "the guy from the diner". Healy recounts a story from a year earlier when a man in a diner was threatening people with a shotgun. Healy stepped in and intervened, causing him to get shot in the arm, but he still managed to beat the crap out of the assailant. It cost Healy a lot in hospital bills, but he claims it was the best day of his life. He then sees that March fell asleep. Healy then drives away and spots Holly reading a book in a dark field. He approaches her and learns that her mother died as a result of a gas leak explosion, which March didn't detect because he has no sense of smell. Holly asks Healy if he killed Blueface. He denies it.
The next morning, Healy and March get ready to continue working, but March is already drinking. Holly calls him out on being a fuck-up and the worst detective ever. Healy mentions the information on the note he found at Shadduck's house, knowing it was written by Amelia. March deduces that the writing isn't for a flight, but for an apartment building. The two drive out to the location, but the building has been torn down for years. They then pass by the Airport Hotel, and the information was for a room number.
Healy and March go into the hotel and ask the bartender if he saw Amelia enter the hotel. After Healy slams his face onto the counter, the bartender says he did see Amelia go upstairs in an elevator, and that "John Boy" may be up there as well. After the two debate on going up there, they take the elevator to the floor where Amelia may be. They find a dying man with his throat cut, and then a man being shot repeatedly until he falls out the window. Healy and March decide to go down. They go back to the car, and March thinks Amelia is dead. To their surprise, she lands feet-first on the car. She tries to shoot at them, but the recoil knocks her off her feet and she goes unconscious.
The guys bring Amelia back to March's home, where Holly is watching TV with her friend Jessica (Daisy Tahan). After Amelia wakes up, she tells them the truth - her mother is behind the murders as a result of the film Amelia made to protest the air pollution from car companies, and Kuttner is doing whatever it takes to stop that film from being shown. The guys then get a call from Tally, who asks them to make a drop with a briefcase full of money. March mentions that Amelia is there, and Tally says she'll send the family doctor over.
Healy and March get the money, but March falls asleep at the wheel and dreams that Healy shows off an ankle gun while a giant killer bee (Hannibal Buress - him again!) is in the back smoking a cigarette. Healy snaps March out of it, but they end up crashing against water barrels, causing the briefcase to fall out and spill the contents everywhere. It's not money, but a bunch of paper clippings.
Back home, Holly answers the door to find a man (Matt Bomer) claiming to be the family doctor to see Amelia. However, Holly quickly figures that this is John Boy. She goes to the cookie jar and takes out her dad's gun. John Boy threatens to cut Holly with his knife. Jessica tries to intervene, but John Boy throws her through the window. The guys make it home as John Boy leaves. He takes a gun out of his trunk and shoots at them. March runs to grab Jessica and brings her in the house. He puts her in the closet to hide with Holly and Amelia. Holly gives March his gun back. Healy shoots at John Boy and runs inside for protection. John Boy flees as he hears police sirens approaching. Amelia escapes out the window and runs into the street. She flags down a car and asks for help. Unfortunately, this is John Boy's car. He shoots Amelia dead and leaves her in the street.
Healy, March, and Holly all feel terrible after Amelia's murder. But a big break in the case happens when Mrs. Glenn reappears. She once again insists that she saw Misty wearing a pinstripe jacket by her window. When Healy mentions he saw that same jacket at Shadduck's house, March gets the idea to go to Mrs. Glenn's house. They see a projector pointed at the window, and Healy mentions seeing the reel for the film at Shadduck's, meaning Mrs. Glenn only saw Misty through the image projected on her window. Mrs. Glenn breaks down because she knows Misty really is dead. The guys realize that there was a second reel, and Amelia was planning on showing it to distributors on that very day at a party.
The guys and Holly attend the party. John Boy and other goons are there to find the film and destroy it. They all learn that Chet is the projectionist. John Boy approaches him and asks where the film is. Healy later finds Chet beaten nearly half to death in a dumpster.
The guys find the room with the projector, but they are cornered by Tally. Holly shows up pretending to be room service and throws coffee in Tally's face, but it's cold and does nothing to her. Tally ends up slipping and knocks herself unconscious, allowing the guys and Holly to get away.
Outside, Holly overhears Older Guy talking to John Boy about their plan. Older Guy spots Holly and brings her back to March at gunpoint on the roof of the hotel. March tells Holly to duck and he whacks Older Guy over the head. March grabs Older Guy's gun and shoots him three times. He tries to grab Holly as he falls, but March pulls her away and falls off the roof. March lands in the pool while Older Guy splatters on the concrete.
The film starts playing for the whole party to see. It features Misty's character speaking against the head of the car company, Bergen Paulsen (Gil Gerard). Paulsen sees it and orders his men to find the film. Holly finds the film first as Tally wakes up. Holly rolls it out the window, leading Healy, March, and the villains to go after it. After a long chase, March ends up with the film, while Healy fights John Boy. Holly walks in on Healy strangling John Boy. She vows to never speak to him again if he kills John Boy. Healy lets go and only knocks John Boy's lights out. The police show up moments later.
Healy and March go to the Department of Justice building to confront Kuttner one last time. She shows no remorse for her daughter's death, and while she knows she's going to jail, she promises that someone worse than her will be in charge next.
Later on, March goes to meet Holly and Healy at a restaurant. He sits with Healy at the bar where they discuss their case, and March thinks that they'll be driving electric cars within five years. He then tells Healy that they have another case, in which a woman thinks her husband is sleeping with Linda Carter (possibly Wonder Woman, possibly not). March has even come up with a name for their agency: "The Nice Guys".