A special U.N. court in The Hague, Netherlands, found the 70-year-old guilty of genocide over his responsibility for the Srebrenica massacre, in which more than 7,000 Bosnian Muslim men and boys were executed by Bosnian Serb forces under his command.
Karadzic, former leader of the breakaway Serb Republic in Bosnia, is the highest-ranking political figure to have been brought to justice over the bitter ethnic conflicts that erupted with the collapse of the former Yugoslavia.
After the verdict, thousands of Serbian ultranationalist supporters of Karadzic took to the streets of Serbian capital of Belgrade, carrying images of the former leader and saying he was being punished for being a Serb.
On the streets of Belgrade, people voiced mixed reactions to the sentence.
"He was given 40 years, did not get a life? So it's a disaster," one man said.
Another said, "They should charge other people, not Radovan Karadzic. He defended Serbian people, sacrificed himself for Serbian people, but authorities in Serbia sent him to Hague."
Prosecutor Serge Brammertz said in a statement that the verdict and sentence "will stand against continuing attempts at denying the suffering of thousands and the crimes committed in the former Yugoslavia."
"Moments like this should also remind us that in innumerable conflicts around the world today, millions of victims are now waiting for their own justice," he added. "This judgment shows that it is possible to deliver it."
U.N. Secretary General Ban Ki-moon hailed the verdicts as a "historic" result for the people of the former Yugoslavia and for international criminal justice, while the U.N. high commissioner for human rights, Zeid Ra'ad Al Hussein, said they exposed Karadzic as "the architect of destruction and murder on a massive scale."
Karadzic, a former psychiatrist, was found guilty of 10 of the 11 charges against him, including extermination, persecution, forcible transfer, terror and hostage taking.
In a statement, the tribunal said it found Karadzic had committed the crimes through his participation in four "joint criminal enterprises," including an overarching plot from October 1991 to November 1995 "to permanently remove Bosnian Muslims and Bosnian Croats from Bosnian Serb-claimed territory."
The trial was heard by the International Criminal Tribunal for the former Yugoslavia
-- an ad hoc court the United Nations established to prosecute serious crimes committed during the conflicts in the former Yugoslavia.
John Dalhuisen, Amnesty International's director for Europe and Central Asia, said the results confirmed Karadzic's "command responsibility for the most serious crimes under international law carried out on European soil since the Second World War."
The Croatian government hailed the verdicts Thursday -- which came at the end of an eight-year trial -- as welcome but long overdue, calling them "the minimum, for which the victims and their families unfortunately waited too long."
Genocide in Srebrenica
In July 1995, tens of thousands of Bosnian Muslims had sought refuge in the spa town of Srebrenica -- designated a U.N. "safe area" -- as the Bosnian Serb army marched toward them.
But with only about 100 lightly equipped Dutch peacekeepers there for protection, the town was overrun by Serb forces.
Delivering the verdicts, presiding Judge O-Gon Kwon said the tribunal found that about 30,000 Bosnian Muslim women, children and elderly men had been removed to Muslim-held territory by Bosnia Serb forces acting on Karadzic's orders.
Karadzic's forces then detained the Muslim men and boys in a number of locations before taking them to nearby sites, where they were executed by the thousands.
The tribunal found that Karadzic was the only person within the Serb Republic with the power to intervene to prevent them being killed, but instead he had personally ordered that detainees be transferred elsewhere to be killed.
It found he shared with other Bosnian Serb leaders the intent to kill every able-bodied Bosnian Muslim male from Srebrenica -- which amounted "to the intent to destroy the Bosnian Muslims in Srebrenica," the tribunal said in a statement.
Civilians targeted in Sarajevo
Other charges against Karadzic stemmed from the infamous siege of Sarajevo, from 1992 to 1995, during which more than 11,000 people died.
The judge said Bosnian Serb forces had consistently and deliberately targeted civilians in Sarajevo, acts that constituted war crimes and crimes against humanity.
"Sarajevo civilians were sniped while fetching water, walking in the city, and when using public transport. Children were sniped at while playing in front of their houses, walking with their parents or walking home from school," the judge said.
He said Karadzic was "consistently informed" about the targeting of civilians, had allowed it to intensify and used it to exert pressure in pursuit of his political goals.
The judge said the sniping attacks on the civilian population, which instilled extreme fear among the city's residents, could not have occurred without Karadzic's support, and the only reasonable inference was that the former Serb leader had intended murder, unlawful attacks on civilians and terror.
U.N. peacekeepers taken hostage
The tribunal also found Karadzic guilty of taking U.N. peacekeepers hostage in May and June 1995, with the judge calling him a "driving force" behind a plot to put the hostages in key military and other strategic locations to deter NATO airstrikes on the targets.
The judge said the U.N. personnel were also threatened during their detention, with the goal of bringing a halt to the strikes altogether.
Karadzic was found not guilty on one of the counts of genocide, relating to crimes against Bosnian Muslims and Croats in "municipalities" throughout Bosnia-Herzegovina.
The tribunal found that Serb forces had killed, raped, forcibly displaced and tortured the other ethnic groups in the municipalities, and found Karadzic guilty of persecution, extermination, deportation, forcible transfer and murder in relation to crimes committed there.
However, the judge said, the court was unable to identify or infer genocidal intent, and therefore couldn't establish beyond a reasonable doubt that genocide had occurred there.
Bizarre path to justice
Karadzic, who had denied the charges against him -- blaming any war crimes committed on rogue elements -- has the right to appeal.
He is also entitled to credit for the time he has spent in custody since his arrest in July 2008.
His road to The Hague has been a long one, marked by bizarre twists. He went into hiding in 1996 and was not arrested until 12 years later. When he emerged, he was heavily disguised by a white beard, long hair and spectacles.
Serb officials revealed that Karadzic had been hiding in plain sight -- working in a clinic in Belgrade, the capital of Serbia, under a false identity as a "healer."
He had also managed to publish a book of poetry during his time on the run.
He was extradited to The Hague to face charges and pleaded not guilty. He initially tried to represent himself, leading to delays in his trial, but eventually was forced to accept an attorney.
Thursday's verdict comes more than a year after the end of his trial in 2014. The 500-day trial included evidence from 586 witnesses and more than 11,000 exhibits.
Karadzic's former army chief, Ratko Mladic
, who was arrested in 2012, is facing charges of genocide and war crimes committed during the conflict. A judgment in his case is expected in 2017.