Prosecutors say Karadzic orchestrated a campaign to destroy the Muslim and Croat communities in eastern Bosnia to create an ethnically pure Serbian state.
The campaign included the 44-month siege of the capital Sarajevo and the torture and murder of hundreds of prisoners in inhumane detention camps.
Al Jazeera's Erica Wood reports on Karadzic's numerous efforts to delay his trial
It culminated in the massacre of some 8,000 Muslim males in one week in July 1995 in the Srebrenica enclave, the worst bloodbath in Europe since the second world war.
Karadzic "harnessed the forces of nationalism, hatred and fear to pursue his vision of an ethnically segregated Bosnia", Alan Tieger, the prosecutor, said in his opening statement last October.
From past remarks and the numerous motions he has filed to the court, Karadzic's main contentions are that Bosnia's Serbs were being persecuted and murdered by Muslims while the West betrayed the Serbs, secretly violating a Balkans arms embargo to smuggle weapons to their enemies.
Karadzic is the most important figure to be brought to trial since Slobodan Milosevic, the former Yugoslav president, who died of a heart attack in 2006 before his case was concluded.
First indicted in 1995, Karadzic eluded a Nato manhunt for more than a decade before being caught in July 2008 in Belgrade, where he had been living as a new-age philosopher.
Representing himself despite his lack of legal training, he has persistently tried to stall the trial, arguing that he did not have enough time to study more than 1 million pages of trial documents and that he was denied enough funding from the tribunal to pay an adequate legal staff to research his defence.
But on Friday, the three-judge tribunal dismissed his request to adjourn the trial until June after his two-day opening statement, and ordered prosecutors to present their first witness on Wednesday.
The UN Security Council, which set up the tribunal in 1993, has ordered it not to open new cases.
The tribunal has indicted 161 political and military officials, of which 40 cases are still continuing.
Two fugitives, Karadzic's former top general, Ratko Mladic, and Croatian Serb leader Goran Hadzic, could still be brought to trial at The Hague.