In the early 1980s, Yuri Orlov (Nicolas Cage), the eldest son of a family of Ukrainian refugees, is visiting a Brighton Beach restaurant, where he witnesses a Russian mobster kill two would-be assassins holding Kalashnikov assault rifles. He is inspired to go into the arms trade, comparing the constant need for weapons to the similar human need for food. After completing his first sale, Yuri convinces his brother Vitaly (Jared Leto) to become his partner. They leave their family’s restaurant behind and go into business together.
Yuri’s first big break comes in the 1982 Lebanon War, when he sells guns to all sides of the conflict, despite witnessing war crimes and atrocities. As Yuri becomes more successful in the war’s aftermath, his business comes to the attention of Interpol and in particular idealistic agent Jack Valentine (Ethan Hawke). Valentine represents a unique threat to Yuri because he is after glory, not money, and thus cannot be bought off.
Vitaly becomes addicted to cocaine after a Colombian drug lord uses drugs to pay for an arms deal. Yuri checks Vitaly into drug rehabilitation and continues his business alone. He lures childhood crush Ava Fontaine (Bridget Moynahan) to a false photo shoot, where they fall in love and subsequently get married.
Following the dissolution of the Soviet Union, Yuri flies to Ukraine and illegally buys tanks and weapons through his uncle, a former Soviet general overseeing a newly-independent Ukrainian Army arsenal with a massive surplus now that the Cold War is over. Yuri then expands to Africa and begins a business relationship with Andre Baptiste Sr. (Eamonn Walker), a ruthless dictator waging a never-ending civil war in Liberia. During one flight into Africa, Yuri’s cargo plane is intercepted by Valentine and forced to land. Yuri escapes arrest by landing in a remote area and distributing the aircraft’s illegal cargo to the locals. Unable to charge Yuri, Valentine tells Ava he is an arms dealer, prompting her to confront him and demand he stop his illegal business. For a time, Yuri complies and does his best to find alternate, legal ways of doing business, but Andre Baptiste Sr. visits him personally, offering a staggering sum in diamonds if he will return to black market arms dealing. Unable to refuse, Yuri agrees.
Yuri convinces Vitaly to come along on a sale in Sierra Leone in 2001, where a militia force allied with Baptiste is visibly preparing to destroy a refugee camp. Sympathizing with the refugees, Vitaly pleads with Yuri to abandon the deal, but Yuri refuses, arguing that if they do the militia will also kill them. Stricken with guilt, Vitaly steals a pair of grenades, destroying one of the weapon trucks and killing Baptiste Jr. Vitaly is shot and killed when the militia retaliate. Yuri reluctantly accepts half of the original diamond payment for the remaining weapons.
Yuri ships his brother’s remains back to the United States. He pays a doctor to forge a phony death certificate and to remove the bullets from Vitaly’s body, but one bullet remains, and Yuri is stopped by the ATF. Meanwhile, while being followed by Jack Valentine, Ava finds Yuri’s security container, finally establishing the definitive proof of Yuri’s guilt. Ava also finds the container full of her paintings, which Yuri secretly bought. Ava takes their son and leaves him. When Yuri calls his parents, his mother says, “Both my sons are dead.”
Valentine detains Yuri and tells him that he has a long jail sentence ahead of him, but Yuri abruptly brings him back to reality. In a forward statement, he tells Valentine that there will be a knock at the door, that a high-ranking military officer will be standing outside, and that he will order Yuri’s release. Yuri explains this by pointing out that some of his customers are enemies of the US’s enemies; that the US President, “who ships more merchandise in a day than I do in a year,” sometimes can’t be perceived as supplying them, and that Orlov’s services in those cases are invaluable to US foreign interests. Valentine then hears a knock at the door. Realizing Yuri was right, he states, “I would tell you to go to hell, but I think you’re already there.” Valentine answers the pending knock and Yuri is released just as he predicted.
Yuri soon returns to the arms trade, going on a trip to the Sahara Desert, “Doing what I do best.” The film concludes with a statement on the screen how the largest arms producers in the world are the US, UK, Russia, France, and China who also are the five permanent members of the United Nations Security Council.