The first former head of state to stand trial before an international tribunal, Milosevic, denounced the accusations as "unscrupulous lies".
Acting as his own lawyer, Milosevic told the court that he needed more than the 150 days allotted to him to cross-examine more than 1600 witnesses whom he has said he intended to call to the stand.
Rejecting the prosecution's claim that he masterminded the bloody wars that tore apart the Yugoslav federation in the early 1990s, he said in his opening defence statement that the international community was "the main force for the destruction" of the country.
He also blamed "the NATO pact" for the conflict in Kosovo, a province of his native Serbia, where more than 10,000 people died and about 800,000 ethnic Albanians - one-third of the population - were expelled in 1998 and 1999.
Observers say his defence is likely to be purely political, rather than specifically focusing on the charges of genocide, war crimes and crimes against humanity that he faces.
He will try to cast himself as a peacemaker and blame the wars on Western powers, as he has done many times during the trial.
The former Yugoslav leader was initially due to present his defence in July, but judges postponed the opening statement because of renewed concern over his high blood pressure.
His continuing ill health, which doctors say could culminate in a heart attack under stress, caused the court to announce a "radical review" of the trial in July.
Up to 200,000 people were killed
in the war in Bosnia
Already the trial has been interrupted over a dozen times after the defendant fell ill and is not expected to end until late 2005.
After his opening statement for which he has been allotted four hours, the judges will discuss plans to force Milosevic -who is representing himself in court - to take on a defence lawyer to lighten his work load. This procedural hearing is likely to take place on Wednesday.
The former Yugoslav president is charged with more than 60 counts of war crimes and crimes against humanity for his alleged key role in the 1991-95 war in Croatia, the 1992-95 war in Bosnia and the Kosovo conflict in 1998 and 1999.
For the bloody war in Bosnia that left 200,000 people dead, he has been charged with genocide and complicity in genocide. If convicted, he faces a life sentence.
Milosevic has so far been acting as his own lawyer although he does have a substantial legal team to assist him behind the scenes.
He argues he does not have to appoint counsel to defend him in a court he deems illegal and has announced he will not cooperate with any lawyer the judges impose.
The prosecution has pressed for the court to impose counsel on the defendant whom they accuse of "hijacking the trial to his agenda while stopping just short of obstructionism".
Milosevic has said he wants former
US President Bill Clinton to testify
The judges will discuss these submissions and go over several medical reports that they ordered, to determine if the one-time Serb strongman is fit enough to continue representing himself.
Milosevic has been given 150 trial days to present his defence, but he has repeatedly complained that he needs more time.
His legal advisers told the New York Times that they had cut back their witness list which originally named more than 1600 people.
The former president said during a procedural hearing he planned to call British Prime Minister Tony Blair, German Chancellor Gerhard Schroeder and former US President Bill Clinton.
His advisers would only say former Greek Prime minister Constantine Mitsotakis and his former Russian counterpart Yevgeny Primakov were on the list of confirmed witnesses.
The first defence witness will be called on 7 September, but the court has not revealed who it will be.