The movie begins with a video being shot of men with their hands tied behind their backs. An enforcer, who we learn later is Lado (Benicio Del Toro) wears a skull Lucha libre mask and runs a chainsaw.
Next, there is a shot of an attractive young blonde woman named 'O' (short for Ophelia, played by Blake Lively) as she narrates in a voice-over. The love of her life is two men: Ben (Aaron Johnson) and Chon (Taylor Kitsch). To her, Ben is like warm wood, the idealistic Buddhist; Chon is steel, the baddist. O is in a polyamorous relationship with both men, and the three live together in Laguna Beach, California in a luxurious cliff-side house for which Ben paid with cash. Ben and Chon are high school buddies. Ben went to Berkeley and majored in business and botany. Chon was a Navy Seal with tours of duty in Iraq and Afghanistan. One day, lounging on the beach, Ben asks Chon where you can get the best weed. Chon replies Afghanistan, and during a tour there, smuggles out hashish/marijuana seeds from which Ben grew in a greenhouse, using his scientific knowledge, cannabis with a THC yield of 33%, "the best in the world." They met O when they hired her to help with managing the greenhouse. Ben is the businessman who runs the production and distribution and handles 99% of the business, while Chon handles the 1% (enforcement). Ben's philosophy is to provide what people want, but Chon is the realist in seeing the money made from marijuana. Ben does a lot of humanitarian work, and sells to marijuana clubs and dispensaries, for medical usage, but most of the money is made from selling on the street, which costs about $6,000 a pound.
After making love to O, Chon sees on his computer an e-mail. The e-mail has a video of Lado kicking around the decapitated heads and reads: "These guys were stupid. Be smarter We need to talk." O and Chon greet Ben returning from a volunteerism trip to Africa. Chon and Ben discuss the business. Ben wants to give up the business to the Mexican cartel as he wants to go into philanthropic ventures such as making $10 solar panels, and he admits he's afraid of the cartel. But Chon argues that selling would show weakness, and once they do this, the cartel would usurp their whole lives.
We see Lado and his 'gardening crew' carry out a hit. Lado accosts a middleman in his home. The middleman pleads forgiveness and promises an even better deal than paying up. He calls El Azul (Joaquin Cosio) (Spanish for The Blue), a cartel head honcho, to connect him with Lado, but Lado shoots the middleman and has a teenage cartel-member-in-training, Esteban, shoot the middleman's wife, while El Azul is on the phone, enraging him. The gardening crew smuggles the bodies out of the house in trash bins. We learn that El Azul is a former inside man with the Baja cartel, the cartel Lado works for. The head of the Baja cartel, Elena Sanchez (Salma Hayek), had a falling-out with El Azul, and now El Azul is encroaching on the Baja cartel's territory, threatening to take over her position.
Meanwhile, Ben and Chon meet with Dennis (John Travolta), a corrupt DEA agent on Ben and Chon's payroll. Dennis tells them about the Baja cartel: they want Ben and Chon's market to fill a market they don't have. Dennis urges them to take the deal instead of decapitation; he reminds them that times are changing and they need to adapt. Dennis is sympathetic to them because his wife has cancer and Ben provides him with his cannabis to ease the effects of chemotherapy.
Ben and Chon go to a hotel room and meet with Alex (Demian Bichir), the representative for Elena. The meeting is secretly video-recorded by Lado, with the video feed shown to Elena in her Tijuana compound.
Alex lays out the deal: a contract of three years of working together, during which the cartel will learn Ben's horticulture methods while providing vast distribution networks and the operation in a safe haven on an Indian reservation that the cartel owns. (The Indian reservations are considered out of U.S. jurisdiction.) During the meeting, Chon badmouths the cartel's products by saying "I think, basically, you want us to eat your shit and call it caviar." Ben and Chon step out into balcony to discuss. We see that a formidable security apparatus, a team of Chon's ex-Navy Seal friends, who have sniper wares trained on the hotel room, backing them. Chon had planned to take out Alex and his men, but Ben talks him out of it. Ben and Chon reach a decision. They will turn over their business to the Cartel, but not join them. The cartel is not happy. (Apparently, no one says 'no' to the Baja cartel.)
Fearing the consequences of their decision, Ben meets with his money guy, Spin (Emile Hirsch), an ex-Goldman Sachs banker who launders and invests the marijuana company's money. Ben wants to set up funds to disappear for three years in Indonesia. Ben, Chon, and O have dinner and discuss the plan for their new lives. Unbeknown to them, they are being watched in the restaurant by Lado's crew. The three celebrate by getting high in their beach house and having a threesome. Lado sits in the car, spying them. He calls Elena to update the situation. Elena says she needs Ben and Chon to join her for their expertise. Hearing about their living situation, she found their weakness: O.
The next day, the three prepare to leave for Indonesia. O wants to do a last minute shopping trip and Chon assigns someone from the security team for her. O is driving to South Coast Plaza (an upscale mall in Orange County), but one of Lado's men intercepts the bodyguard and kills him. They tail O. In one scene, O is shopping next to a girl who is talking on a cellphone, answering her mom's questions about college life. Her mom turns out to be Elena.
Returning home but not finding O, Ben and Chon hear a chime indicating a Skype call, and to their horror, see a live web feed of the kidnapped O. Elena, her voice masked, reprimands the boys for not complying with the deal. To redress the insult of the cartel's product during the meeting, Elena has Chon put a gun into his mouth, indicating she will tell Lado to cut off O's fingers otherwise. She almost gets Chon to pull the trigger but stops him at the last minute, telling him this will clean up his mouth.
Elena tells Ben and Chon to deliver 300 pounds of their marijuana in five hours to show compliance. They get the product and race to Chula Vista. They arrive just in time despite being almost pulled over (and Chon almost having to kill the highway patrolman). Lado and his men take their car. Ben and Chon drive back in Lado's truck, which contains the suitcase of money (they paid in full, Ben and Chon note) and a cell phone. Elena calls, her voice unmasked, and tells them that she will hold O hostage for one year to make sure they comply with all of her demands. Chon argues with Ben that they have to fight to get O back -- the cartel members are savages who will kill them anyway. But Ben just wants peace and O back.
Ben and Chon meet again with Dennis, who tells them about the conflict between Elena and El Azul. Chon strong-arms Dennis into getting data on Elena and the Baja cartel from the DEA. He is able to get 60 days of financial transactions, encoded onto two credit cards. Dennis also tells them that two of Elena's sons and her daughter (Magdalena), are dead. Back in their company HQ, Ben and Chon have Spin and his experts look into the financial data on the computer. From it, they trace Elena's financial routes. They figure out that one of her real-estate holdings, a trailer house, is a drop off point for the cartel's business. Ben decides on a plan to pay to get O back. He and Elena negotiate to a $13 million ransom. They decide to hijack the drop to get the cash for O's ransom, and make it look like El Azul hit the cartel.
The hijacking goes underway. Wearing masks, Chon and his team of ex-Navy Seals blow up the front car in a convoy with IEDs. When the men from the trailer retaliate, an ex-Navy Seal member takes them out with RPG rockets. Chon forces the men out of the car carrying the cash by putting a grenade in the gas tank. He takes the briefcase from a man scrambling out of the car. Ben is horrified by the killings. One of the cartel members is about to shoot Ben, but Chon shoots the member in the back, spraying blood on Ben's mask. They take the money and get away. Alex and Lado arrive to assess the damage, which is 3 million dollars gone and seven men dead. Lado urges Alex not to inform Elena of the loss because he wants to recover the money and rectify the situation himself and because he fears Elena.
Ben and Chon get a message to have Ben meet with Alex and Lado. Alex and Lado interrogate Ben to find out their whereabouts during the hijacking but Ben plays it cool. He insinuates that it could be Lado's men. After Ben leaves, Alex decides Ben and Chon don't have the balls for the attack. He suspects El Azul but Lado isn't so sure.
We see O at the shack where they are holding her. She is being watched over by Esteban. Her living conditions are bad: one of her legs is chained to a chair, she has a bucket for bathroom and sleeps on a spring bed in a cage. She pleads into the surveillance camera and gets to talk to Elena, and begs her for some concessions. Elena asks O how long she has been using. Since 8th grade, O says, not that her mother cared. Later we see Lado feeding O a steak, and later, giving O a drug fix, and her getting high. O is also given access to a laptop to send a fabricated email to her mother so she won't file a missing persons report on O. Afterwards, Lado tells Esteban, don't look at me like that (because we see later in the movie Lado shows O a cellphone video of him raping her while she was high).
Elena's daughter, Magdalena (Sandra Echevarria) is seen having sex when she is interrupted by a phone call. Her mother is on the line, informing her that she is coming to California to visit. Elena gets on a private plane to the Indian reservation in order to avoid U.S. customs. Lado will follow her later, bringing O with him. Before boarding the plane, Lado tells Esteban that he's proven too sensitive to handle the work and proceeds to shoot and kill him.
Upon arrival to California, Lado brings O to Elena. Elena immediately informs Lado that she knows about the hijacking, and chastises him for not telling her. She threatens Lado to recover the money and he informs her that he didn't tell her because he was trying to get proof that Ben and Chon were behind the hijacking.
Ben has Spin fabricate documents and hack into Alex's bank accounts to frame Alex as the mole to El Azul. Ben confronts Lado with Alex's dossier in an effort to take the heat off of him and Chon. To save himself, Lado visits El Azul and makes a deal to work with him.
At a posh spa, Elena and O have dinner during which we learn that Elena inherited the business after her husband was killed. Her twin sons and brothers are also killed, leaving two children who resent her and do not want her in their lives (her daughter and a third son). Elena tells O she likes her, but won't hesitate to kill Ben and Chon. When O remarks that only she can 'get Ben and Chon together,' Elena scoffs, telling O that her love story has a serious problem: Ben and Chon must love each other more than O because otherwise, they wouldn't share her.
Later, Lado brings Ben and Chon to see Alex being whipped. The torture is video-fed to Elena who forces O to watch once he 'confesses.' Under the threat of his family being harmed, Alex confesses to working with El Azul. He begs Elena for forgiveness, citing the names of her husband and children. Lado douses Alex with gasoline and anoints Ben to be the executioner. To go through with the falsehood, Ben ignites Alex on fire. O watches in horror.
The next morning, Ben and Chon walk along the beach where they discuss the night's events. Chon tried to justify what Ben did by referring to the Dalai Lama, but Ben brushes it off. Instead, he tells Chon that during Alex's plea to Elena, Alex swore on Magda's life; meaning that Elena's daughter is alive, and that Dennis knew this and hid it from he and Chon. They make a plan that will work even faster than accumulating the money for ransom: kidnap Elena's daughter and trade her for O.
Lado pays Dennis a visit at his home. It turns out Lado also has Dennis on the payroll. Lado questions Dennis on the cluprits behind the hijacking and Dennis assures him it was Azul. Lado informs Dennis that it can't be Azul because he's working with him now instead of Elena. Under threat, Dennis reveals that the hijackers are Ben and Chon, but that they are going to give the $3 million to Elena and not Lado. To head off Elena, Dennis tells Lado to kidnap Magda and sell her to Ben and Chon. Dennis is incredulous to learn that Elena is on U.S. soil.
Dennis meets with Ben and Chon, who chew him out for giving them away to Lado. The boys offer Dennis the $3 million they stole in exchange for Magdalena's address. They kill her bodyguard, who is sitting outside her dorm in his car, then move inside, tying up her boyfriend and kidnapping her. Wearing masks as a show, they Skype with Elena and show a shivering Magda, tied up and stuffed in an ice box. Elena meekly agrees to their demands. At the end of the talk, O informs Elena that she knew her boys would come for her. Elena slaps O, then screams at everyone to get out. She drops to the ground, rips off her wig, and breaks down.
Lado and his boys take O into another room, where she is chained to a chair. Lado makes everyone else leave the room, then he shows her the video he took when he raped her while she was drugged. She spits in his face, but he enjoys it, wiping himself off on her hair.
Elena's SUV and Ben and Chon's SUV meet in an open field with their hostages. On the mountain ridges, each group has their sniper team in position. Elena steps into the open with O and releases her. O runs to Ben. Ben and Chon release Magda to Elena, who tells her mother that she will never speak to her again. Before Elena returns to her car, she asks Chon who the rat is. Chon smiles and nods toward Lado, who blows back a kiss. Elena turns around to shoot Lado, but Lado draws his gun and shoots her first. O, who was handed a gun by Ben, makes her way to Elena and wants to kill her, but relents when she sees Elena is already dying. Elena begs O to help Magda escape. O glares at Magda briefly before hustling her to safety.
A massive shootout is underway. Each group's sniper team shoots at each other, taking out some members of each team. Chon kills Elena's bodyguards and Ben and Chon converge on Lado, hiding behind the SUV. Ben shoots Lado three times in the back, but Lado turns around to shoot Ben in the throat. Lado sprawls on the ground, severely wounded. O shoots Lado dead in vindication, and erases his phone. O rushes to Ben, seeing his wound is lethal. As O cradles Ben, Chon pulls out a syringe and injects Ben, O, and then himself with drug overdoses. They die in a triple suicide. "That's the perfect ending," O narrates while looking into the sky as she dies.
But wait... Rewind, as O mentions that this was just how she imagined it.
What really happened, as O narrates, "was more of a fuck-up than a shootout." After Elena steps out into the open and releases O, Lado retreats to the car and drives away. A helicopter and DEA agents led by Dennis swoop in to arrest Elena. The DEA agents disarm the sniper teams and arrest everyone (including Ben, Chon, and O).
O narrates as we see a montage: Dennis is grandstanding on TV about Elena's arrest and the progress on the war on drugs (Indian grounds are still U.S. grounds he says); Elena goes to prison for 30 years, while Ben and Chon, who have enough information to put Dennis away, are released after a few weeks in a holding cell after Dennis said that they were confidential informants. Lado and El Azul form a new cartel to take over the vacuum left by Elena.
After their release, O says that she, Ben, and Chon all vanished. Montages are shown of them living new lives in Indonesia, Africa, and other parts of the world. A few scenes show that they continue to remain in touch and get together, but most of the scenes strongly imply that for the most part, they've all gone their separate ways-- as O narrates, perhaps it's true that three people can't all be equally in love. She says that one day, perhaps they'll return to their pot business in Laguna, but for now, they live simple, even primitive lives, like 'beautiful savages.'