- After splitting with the Joker, Harley Quinn joins superheroines Black Canary, Huntress, and Renee Montoya to save a young girl from an evil crime lord.
- A twisted tale told by Harley Quinn herself: When Gotham's most nefariously narcissistic villain Roman Sionis, and his zealous right-hand, Zsasz, put a target on a young girl named Cass, the city is turned upside-down looking for her. Harley, Huntress, Black Canary, and Renee Montoya's paths collide, and the unlikely foursome has no choice but to team up to take down Roman.
- After her painful breakup with Joker, shortly after the battle with the Enchantress in Suicide Squad (2016), the already unhinged and extremely volatile Harley Quinn finds herself all alone. But with her mentor out of the picture and a huge target on her back, Harley locks horns with Gotham City's ruthless crime lord Roman Sionis, who's trying to track down a precious diamond and the audacious pickpocket, Cassandra Cain. Now, on the hunt for the teen street hustler and the gemstone, Quinn crosses paths with singer Dinah Lance, Detective Renee Montoya, and a mysterious crossbow-wielding murderess who are all also after Cassandra, as Roman's top assassin, Victor Zsasz, is bent on getting her first. Can Harley take down the brutal super-villain known only as the Black Mask?—Nick Riganas
- In Gotham City, the Joker breaks up with Harley Quinn and without his protection, several criminals that have a beef with her hunt her down. When teenager Cassandra Cain pickpockets a diamond that has the account numbers of a fortune from the gangster Victor Zsasz, who is the right-hand of the powerful criminal Roman Sionis, he put a contract on her. Harley Quinn, Police Detective Renee Montoya, Helena "The Huntress" Bertinelli. and Dinah "Black Canary" Lance team up to protect Cassandra.—Claudio Carvalho, Rio de Janeiro, Brazil
- The film starts with Harley Quinn (Margot Robbie) telling her story from the beginning through an animated intro. As a child, her deadbeat alcoholic dad tried to get rid of her multiple times until he finally dumped her at a Catholic girls school. Harley was always a troublemaker, but she got educated and earned a PhD, becoming a psychologist. That's where she met The Joker and fell in love, leading her to go from Harleen Quinzel to Harley Quinn. However, they have recently broken up since he helped her escape from prison (shown at the end of the previous film 'Suicide Squad'), and despite Harley saying she was fine, she does not take it well and ends up staying alone in a crummy apartment with a hyena she adopted and named Bruce (after Bruce Wayne).
Harley goes to the Black Mask club where she gets plastered (drunk) and annoys a nearby thug who insults her. She ends up smashing his leg, and is told by the club's owner, Roman Sionis/Black Mask (Ewan McGregor), that that was his driver. He does nothing because Harley hasn't told anybody that she and Joker are broken up, since them being a couple gave her immunity from the wrath of Gotham's other thugs. Harley is out with other women whom she overhears saying that she's nothing without Joker and that she'll go running back to him soon enough. Harley decides to challenge this by driving a truck into Ace Chemicals where she and Joker used to stay, obliterating the plant into an explosion of fireworks.
Moments before this, Detective Renee Montoya (Rosie Perez) is investigating what appears to be a mob hit at a restaurant. A flashback shows Helena Bertinelli/Huntress (Mary Elizabeth Winstead) killing the men inside with a crossbow, which has earned her the alias, "The Crossbow Killer." Montoya then hears the chemical plant explosion and goes to find Harley's J necklace, which is a clear sign to both cops and criminals that she and Joker are no more, meaning Harley has just declared open season on herself.
Among the criminals that want Harley dead are Roman and his best friend/right hand man Victor Zsasz (Chris Messina), a psychopath who carves a tally on his body for every one of his victims. They are shown torturing the Keo family and cutting their faces off.
Harley is getting her "perfect egg sandwich", but Montoya and a few other pissed off crooks find and go after her. Montoya tackles Harley and causes her to drop her sandwich into the street, which devastated Harley. When it seems like she's cornered, she throws a bag of garbage at Montoya, which blindsides one crook and causes him to shoot an incoming truck-driving crook, allowing Harley to get away. Unfortunately, she runs into a large thug that she and Joker face-tattooed, but before he can get her, he is killed by Helena on her motorcycle. Harley is then surrounded by Roman's thugs.
Montoya returns to the police station where she is mocked by other officers. She meets with Captain Patrick Erickson (Steven Williams), who was her former partner that took credit for her hard work and got promoted, and District Attorney Ellen Yee (Ali Wong), who is also Montoya's ex. She is building a case against Roman but doesn't have much support from either of them. Montoya is then brought to Cassandra Cain (Ella Jay Basco), a young girl brought in for pick pocketing. Montoya then gets a call from Dinah Lance/Black Canary (Jurnee Smollett-Bell), saying that Cass has a diamond with her. Soon, Harley comes in and tries to go after Cass, but she realizes she is getting ahead of herself in the story.
A week earlier at the club, Roman was telling Mr. Keo (Francois Chau) about the Bertinelli Diamond, which contains codes to their massive fortune and is now in Roman's possession. The diamond was also the reason Helena's whole family was slaughtered. Keo refused to work with Roman, which is what later leads to the demise of him and his family. Dinah works at the club as a singer, noted for her beautiful voice. She later talks to a drunken Harley, who admits to her that she and Joker broke up. Harley then drinks with another man who later tries to abduct her. Dinah sees this and beats up the man and his buddies. Roman observes this from his window and is impressed, and he has Zsasz bring Dinah up so he can hire her as his new driver. This leads Montoya to try and get info from Dinah on Roman, but she refuses to help.
Dinah knows Cass because they live in the same building, and Dinah has a soft spot for Cass since she knows she lives with abusive foster parents. Later on, Cass picks Zsasz's pocket and steals the diamond, just before she is arrested for other stuff she stole.
Just after Harley gets away from Montoya, Roman's guys capture her. She knows he had a long list of grievances against her (such as "voting for Bernie, pronouncing it 'expresso', and calling him Romey"). Roman smacks Harley around, at which point she has a fantasy about herself as Marilyn Monroe in a "Diamonds Are A Girl's Best Friend" sequence. Before Roman can have Harley killed, he learns from Zsasz that the diamond is gone. Harley offers a chance to recover the diamond, which Roman agrees to. After she leaves, he orders a bounty on Cass.
Cut to Harley attacking the police station with colored smoke and confetti bombs. She breaks Cass out but also lets loose other crooks who want to kill her. Harley fights them all on her own, with a little help from Cass, utilizing a baseball bat and lighter, among other things. More goons who want Cass and the diamond shows up, and after inhaling some coke, Harley kills them. She escapes the station with Cass in tow and takes her somewhere safe.
Roman learns that Harley and Cass got away from his goons. He loses his shit and spots a woman, Erika (Bojana Novakovic), in his club laughing, and Zsasz convinces Roman that she is laughing at him. He orders Erika to dance on the table and to take off her dress, going as far as to order her friend to cut it off of her. This shows Dinah just how monstrous Roman is.
Harley learns that Cass swallowed the diamond and goes to a supermarket to buy laxatives, warning her that anyone else will have no problem cutting it out of her. They rob their supplies and go back to Harley's apartment, which is above a Taiwanese restaurant run by Doc (Dana Lee), a kindly man who keeps Harley safe. After Harley and Cass go upstairs, Helena approaches Doc to ask for Harley. Harley then cuts to Helena's backstory: after her family was murdered by mob boss Stefano Galante (Roberto Catrini), one of Galante's goons saw that she survived but took her away to Sicily to stay with his brother and father. They trained Helena to become the killer that she is now. She killed Galante, and the mob guys from earlier were the firing squad that killed her family. Zsasz is the last name on her list.
Back at the police station, Montoya finds out that Yee went behind her back and told Erickson that she stole evidence from a crime scene. Erickson suspends Montoya.
Harley's apartment comes under attack by one of Roman's goons. The place gets blown up, and Bruce goes missing. Harley learns that Doc sold her out to Roman's goons because they paid him well. Harley then contacts Roman and offers to trade Cass in exchange for immunity. He agreed and has Dinah drive Zsasz to meet them, but Zsasz spots a text exchange between Dinah and Montoya to let her know where they are headed. He informs Roman, who becomes upset and puts on his Black Mask.
Harley arranges to be met at an amusement park in a spot called the Booby Trap where she used to hide with Joker. Cass learns about the betrayal as Harley straps her to a toilet so she can pass the diamond. Montoya shows up first and fights Harley, nearly taking her in until Harley uncuffs herself and kicks Montoya out of the building. Dinah and Zsasz show up, but Zsasz hits Harley with a tranquilizer and prepares to kill her. Helena shows up and shoots Zsasz in the neck with an arrow, killing him. The ladies then confront each other until they see Roman show up outside with a whole army of thugs. Knowing that he has a bone to pick with all of them, Harley suggests they team up to fight them all. They reluctantly agree and grab a bunch of old weapons (mallet for Harley, bat for Dinah, brass knuckles for Montoya, etc) and head off to fight. They smash and bash their way through a bunch of goons before Roman manages to kidnap Cass. The ladies are cornered by armed goons until Dinah lets out a supersonic scream to take them down and allow Harley to go after Roman on roller blades.
Harley chases Roman and gets knocked over by other goons. Helena rides by and gives Harley a pull, managing to kill those other goons before causing Roman's car to crash. He takes Cass to the pier and tries to taunt Harley, saying she needs him. She hits back that the criminals in Gotham should fear her, not him or Joker. Before Roman can hurt Cass, she reveals she planted a grenade on him and pulled the pin out. Harley throws Roman off the pier where he explodes into bloody chunks before hitting the water. The others join Harley and Cass, relieved that Roman is now gone.
The next morning, the ladies gather for tacos and margaritas. Cass goes to pass the diamond, but she and Harley just steal Dinah's car and ride off.
Later on, Erickson once again takes credit for Montoya's work in bringing down Roman and his empire. She quits the GCPD and joins Dinah and Helena to form the Birds of Prey using the money in the Bertinelli accounts.
Harley and Cass pawn the diamond and ride away with Bruce (who turned up alive), with Harley taking Cass on as her apprentice. Harley says she may be a softie, but she dares anyone else to call her that.
After the credits:
Harley's voice can be heard getting ready to tell the audience a big secret about Batman... only for the audio to cut off.
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