As the judges described the siege of Sarajevo, Karadzic looked pained and his face tightened into a grimace.
Victims' families in the courtroom, some of then elderly, listened intently when the genocide at Srebrenica was discussed. One wiped away tears as the judge described men and boys being separated from their families.
After that, Karadzic stared ahead vacantly. When he was ordered to stand for sentencing, he listened with eyes mostly downcast. After the sentence was read and judges departed, he sat back heavily in his chair.
After the hearing was closed, several victims' families embraced before quietly leaving the courtroom.
Karadzic was arrested in 2008 after 11 years on the run, following a war in which 100,000 people were killed as rival armies carved Bosnia up along ethnic lines that largely survive today.
He headed the self-styled Bosnian Serb Republic and was Supreme Commander of its armed forces. He said in an interview ahead of the verdict that he had worked to uphold peace and deserved praise, not punishment.
"My permanent fight to preserve the peace, prevent the war and decrease the sufferings of everyone regardless of religion were an exemplary effort deserving respect rather than persecution," he told news portal Balkan Insight.
Serbian Prime Minister Aleksandar Vucic said he would stand by the Serbs of Bosnia.
"We will stand by our people and we will protect their existence and their right to have their own state," he said.
ICTY prosecutor Serge Brammertz said the world had decided that victims in the former Yugoslavia deserved justice.
"For two decades now, those victims have put their trust in us to deliver it. Thousands came here to tell their stories and courageously confront their tormentors. Today, with this conviction, that trust has been honoured. Justice has been done."
The only more senior official to face justice before the Tribunal was the late Serbian President Slobodan Milosevic, who died in custody a decade ago before a verdict was reached.
Ratko Mladic, the general who commanded Bosnian Serb forces, was the last suspect to be detained over the Srebrenica slaughter and is also in a U.N. cell awaiting judgment.
Munira Subasic, whose son was among the victims of Srebrenica, said the "verdict is very important to show new generations, especially those in Serbia who have been poisoned with hatred already, what really happened in Bosnia".
The Srebrenica massacre and the years-long Serb siege of Sarajevo were events that turned world opinion against the Serbs and prompted NATO air strikes that helped bring the war to an end.
Karadzic defended himself through his 497-day trial and called 248 witnesses, poring over many of the millions of pages of evidence with the help of a court-appointed legal adviser.
Rejecting the charges against him, Karadzic sought to portray himself as the Serbs' champion, blaming some of the sieges and shelling on Bosnian Muslims themselves. He says soldiers and civilians who committed crimes during the war acted individually.
Opponents of the ICTY say its prosecutors have disproportionately targeted Serbs as 94 of 161 suspects charged were from the Serbian side, while 29 were Croat and nine Bosnian Muslim. [http://tmsnrt.rs/1Sd4TAa ]
Prosecutors have been criticised for not bringing charges against two other leaders of that era who have since died - Croatian President Franjo Tudjman and Bosnian President Alija Izetbegovic.
"If you had got prosecutions of those three (including Milosevic) then you'd get a really good picture of the way the violence was produced but we're not getting it," said Eric Gordy, an expert on the court at University College London.
Many Serbs, both in Bosnia and Serbia, regard the court as a pro-Western instrument, say Karadzic is innocent and believe his conviction would be an injustice for all Serbs.
Their belief is strengthened by the fact that the sentencing coincides with the anniversary of the 1999 NATO bombing of Serbia that led to independence for the ethnic Albania-dominated province of Kosovo.
Prosecutor Brammertz worries that its work, which is winding down, has done little to heal the war's deep wounds.
"I'm not convinced everyone has really understood the wrongdoings from the past," he said.
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