Set against the backdrop of 1950s New York, Motherless Brooklyn follows Lionel Essrog, a lonely private detective afflicted with Tourette’s Syndrome, as he ventures to solve the murder of his mentor and only friend, Frank Minna.
When private detective Lionel Essrog (Edward Norton)’s boss and father figure Frank Minna (Bruce Willis) is murdered while working a mysterious case, he is determined to solve it and avenge his father. He eventually discovers it all leads back to Moses Randolph (Alec Baldwin), who has built most of the city and is driving minority and low-income residents out. Frank discovered Moses’s illegitimate daughter Julia (Gugu Mbatha-Raw) and tried to extort more money for the evidence, and was killed. Lionel is able to cut a deal with Moses to let Julia live and be free or he will release the evidence he’s uncovered, and Lionel and Julia move out of the city to a house that was left to him by Frank.
In the 1950s in New York City, Lionel Essrog (Edward Norton) works a detective agency alongside Gilbert Coney (Ethan Suplee), Danny Fantl (Dallas Roberts), and Tony Vermonte (Bobby Cannavale). Their boss, Frank Minna (Bruce Willis), found them when they were being raised in the orphanages and rescued them, and now they all work for him. Lionel is kind and smart, but also plagued by Tourette’s syndrome which makes him seem strange and as such he leads a fairly isolated life. But alongside his Tourette’s also come things like perfect recall and memory which make him good at detective work.
Frank has been at work on a secret job and is taking a big, secret meeting for it – he asks Lionel and Gilbert to shadow him in case it goes south. Lionel listens over the phone as Frank presents some important information that is threatening some sort of big deal to a group of men – William Lieberman (Josh Pais), Lou (Fisher Stevens), and an extremely large henchman. They ask Frank where the original copies are, and Frank tries to negotiate a high price for them, so the men drag him out to force him to take them to the originals. Lionel and Gilbert follow in their car, and arrive just in time to see Frank being shot. He tells them he led the goons on a goose chase and made a run for it – they take him to the hospital but it’s too late, and Frank dies.
Frank’s widow Julia (Leslie Mann) leaves Tony in charge of the office. Lionel, determined to find out what Frank was working on and who killed him, begins wearing Frank’s hat and coat and starts investigating. He finds a matchbox in Frank’s coat pocket and goes to check out an African-American bar. Piecing together a few of the words he heard on the phone call, he realizes that whatever Frank found, it involved Julia Rose (Gugu Mbatha-Raw), a young woman working for Gabby Horwitz (Cherry Jones). Gabby and Julia are fighting gentrification in the city – poor and minority neighborhoods are being bought out and demolished and their inhabitants forced out of the city. Lionel goes to a council meeting and sees Moses Randolph (Alec Baldwin), who the city folk blame for this problem. He’s the one in charge of development and built half the parks in New York City. Lionel steals a reporter’s credentials and begins asking questions – a man named Paul (Willem Dafoe) who rampaged against Moses in the meeting gives Lionel some tips.
Lionel follows Julia and under the guise of reporting on the gentrification story gets to know her and about the situation. She takes him to the club that Frank was looking into and the two have a dance. Her father (Robert Wisdom), assuming that Lionel is one of Randolph’s men, has his men beat Frank unconscious – a trumpet player at the club (Michael K. Williams), rescues Lionel and lets him stay at his apartment. Frank continues researching, and discovers that Paul is Moses’s brother, and also that Lieberman is getting kickbacks on so many of the housing deals. He also realizes that the housing relocation programs are scams. Meanwhile, Paul, an engineer who is desperately trying to help the city and has been nearly cut off by his unethical brother, presents Moses with a huge renovation plan that will help the city greatly.
Lionel gets a call from Julia’s father, apologizing for the attack and saying he now knows he was one of Frank’s men and he has information for him, but when Lionel goes to meet him at the club, he’s been murdered and staged like a suicide. Julia finds him and is distraught, and so Lionel stays the night in her apartment to keep her company. He admits the truth about who he is and that he just wants justice for his friend Frank, and he believes her to be in danger. He tells her that Frank always called him “Motherless Brooklyn”. When Lionel finds photos of Paul meeting with Julia’s father, he confronts her – she explains that her “Uncle” Paul is her real father, and that she suspected this but they never told her officially. Lionel goes to Paul, and tells him he suspects that this information somehow is trouble for Moses, and he can’t believe that he would put Julia’s life in danger. Paul says that he did no such thing, that Frank and Julia’s father had the idea to get more money out of Randolph’s goons and he told them not to. He begs Lionel to find the evidence.
Randolph’s goons summon Lionel to meet with Moses. He tells Lionel to join his team and stop snooping, and gives him 24 hours to decide. Lionel eventually puts the pieces together and realizes that inside Frank’s hat is the key to a safe deposit box. Inside is the deed to a building, and Julia’s birth certificate: Moses is her father, not Paul. He gives the key to Paul and runs into Tony, who has been working for Randolph doing surveillance. They get a drink, and Tony admits he’s been sleeping with Julia. He tells Lionel to take the deal, since Julia is about to be killed anyway. Lionel throws hot water in Tony’s face and races to save Julia. He stops her just before she enters her apartment, and the two flee and eventually get the upper hand on the assassins: Julia knocks the large one off the fire escape, and Lou corners them with a gun but is hit over the head by the trumpet player, who had witnessed Lionel running in. Lionel has him drive Julia out of town.
Lionel meets with Moses, and asks for his side of the story. Moses raped Julia’s mother, an employee, and this information threatened to destroy everything. Paul signed off on the birth certificate because he’s a man of morals. Moses wants to know what Lionel wants – for him to stop his latest leveling of a poor neighborhood? But Lionel says all his wants is Julia to be left alone, or he will release the information. He also tells him that Lieberstein is on the take, and tells Moses that when he takes Lieberstein out, to tell him it’s for Frank. Moses tells Lionel to tell Paul that his plans are incredible and there’s no reason to deny them. The next day, Moses denies Paul’s plans anyway out of spite. Lionel drives out to the property that Frank left him in the deed, where Julia is waiting for him.