The former Soviet officer was sentenced Thursday in a federal court in Manhattan. He was also fined $15 million.
Russia's Foreign Ministry, who have described Bout's arrest as illegal, called the sentence "unfounded and biased" and pledged on Friday to seek his return home.
Bout had been jailed since his arrest four years ago in Thailand after he met U.S. Drug Enforcement Administration operatives posing as agents of a Colombian terrorism group. He was extradited to the U.S. for trial in 2010.
Prosecutors portrayed Bout as among the world's worst villains. They say the 45-year-old was ready to sell up to $20 million in weapons including surface-to-air missiles to shoot down U.S. helicopters.
Bout has insisted he's a legitimate businessman.
On Thursday, Bout made it clear he had heard enough in court, although a federal prosecutor was only two minutes into an argument urging a harsh prison sentence.
"It's a lie!" Bout blurted out in English — a rare show of raw defiance for a defendant facing a possible life term.
Despite Bout's outburst and his insistence that he was framed, he received only the mandatory minimum 25 years in prison.
The way federal agents went about capturing Bout — an elaborate sting that lured him to Thailand — appeared to play in his favor at his sentencing in federal court.
U.S. District Judge Shira Scheindlin said 25 years — not the life sentence wanted by prosecutors — was sufficient and appropriate because there was no evidence the 45-year-old Bout would have been charged with seeking to harm Americans if not approached by informants posing as Colombian rebels.
"But for the approach made through this determined sting operation, there is no reason to believe Bout would ever have committed the charged crimes," she said.
Bout's sentencing came four years after his arrest in Bangkok, where he was held before his extradition to the U.S. for trial in late 2010, and months after a jury convicted him of four conspiracy charges relating to his support of a Colombian terrorist organization.
For nearly two decades, Bout built a worldwide air cargo operation, amassing a fleet of more than 60 transport planes, hundreds of companies and a fortune reportedly in excess of $6 billion — exploits that were the main inspiration for the Nicholas Cage film "Lord of War."
His aircraft flew from Afghanistan to Angola, carrying everything from raw minerals to gladiolas, drilling equipment to frozen fish. But, according to authorities, the network's specialty was black market arms — assault rifles, ammunition, anti-aircraft missiles, helicopter gunships and a full range of sophisticated weapons systems, almost always sourced from Russian stocks or from Eastern European factories.
In 2008, while under economic sanctions and a U.N. travel ban, Bout was approached in Moscow by a close associate about supplying weapons on the black market to the Revolutionary Armed Forces of Colombia, or FARC.
Bout was told that the group wanted to use drug-trafficking proceeds to pay for surface-to-air missiles and other weapons, making it clear it wanted to attack helicopter pilots and other Americans in Colombia, prosecutors said. He finalized the phony deal with the two DEA informants in a bugged hotel room in Bangkok in March 2008.
Throughout the case, Bout maintained he was a legitimate businessman who wasn't selling arms when the American operatives came knocking.
But in court papers, federal prosecutors said the government initiated its investigation in 2007 because Bout "constituted a threat to the United States and to the international community based on his reported history of arming some of the world's most violent and destabilizing dictators and regimes."
The Merchant of Death moniker was attached to Bout by a high-ranking minister at Britain's Foreign Office, who had drawn attention to his 1990s notoriety for running a fleet of aging Soviet-era cargo planes to conflict-ridden hotspots in Africa.
The nickname was included in the U.S. government's indictment of Bout, and U.S. Attorney Preet Bharara referenced it when he announced Bout's extradition in late 2010, saying: "The so-called Merchant of Death is now a federal inmate."
After the sentencing, Bharara in a statement called the sentence "a fitting coda for this career arms trafficker of the most dangerous order."