In opening statements, prosecutors painted a picture of the former Bosnian Serb leader as a supreme commander single-mindedly pursing a campaign of "ethnic cleansing" during the 1992-95 Bosnian war that killed an estimated 100,000 people.
They spoke to empty chairs on the defendant's side of the court as Karadzic, who denies all the charges, boycotted the trial at the International Criminal Tribunal for the former Yugoslavia in The Hague for a second day.
"The Supreme Commander explained in October 1991 what was coming: 'Sarajevo will be a black cauldron where Muslims will die. They will disappear … from the face of the earth'," the senior prosecutor, Alan Tieger, cited Karadzic as saying in an intercepted call. He was referring to the 43-month siege of Sarajevo that began in 1992 and killed an estimated 10,000 as the former Yugoslavia was torn apart by Serbs, Croats and Muslims fighting for land.
"The supreme commander had directed his forces in a campaign to carve out a mono-ethnic state within his multi-ethnic country," Mr Tieger said. "This case is about that supreme commander. A man who harnessed the forces of nationalism, hatred and fear to implement his vision of an ethnically separated Bosnia – Radovan Karadzic."
As prosecutors began their case yesterday, Biljana Plavsic, Karadzic's successor as Bosnian Serb president, left a Swedish prison and arrived in Belgrade after winning early release from her sentence for committing war crimes.
Karadzic, 64, has denied 11 war-crimes charges arising from the violent break-up of Yugoslavia, including two charges of genocide for the massacre of 8,000 Muslim men and boys at Srebrenica and for broader atrocities.
Karadzic, a psychiatrist before becoming president of the self-proclaimed Republica Srpska, stepped down from power in 1996 and went into hiding until he was captured in July 2008, disguised as an alternative healer in Belgrade.
He had battled judges during pre-trial proceedings, seeking immunity and more time to prepare for trial, which was denied as judges pressed forward with plans to begin the case.
Karadzic is the court's highest-profile defendant since former-Yugoslav president Slobodan Milosevic, whose trial ended with his death in 2006.
Milosevic also obstructed proceedings to buy time and gain concessions from the court.
Ahead of opening statements, Judge O-Gon Kwon issued another warning to Karadzic to appear in court or risk having counsel assigned to him and being tried in absentia. "Should the accused persist in his refusal to attend … the trial will proceed in his absence," the South Korean judge said, adding that the court would decide after the opening remarks end on Monday.
"If we get enough time to prepare a proper defence, he will appear in court, definitely," said Marko Sladojevic, one of Karadzic's legal advisers, adding that the accused was following proceedings closely, working until 5am on the trial.
A mother who lost much of her family in Srebrenica condemned his absence.
"Today again the war criminal Karadzic did not appear at his trial," Nirmela Kolenovic said. "For me, it means he is a coward and he has acted in a cowardly manner towards the Serbian people."
The trial is expected to last years and involve hundreds of witnesses.