Momir Pelemis and Slavko Peric were detained in the eastern town of Zvornik, officials say.
Prosecutors accuse the two men of taking part in the arrest and execution of up to 1,700 civilians in Srebrenica.
In all, some 8,000 Muslim men and boys were killed when Bosnian Serb troops overran the town in July 1995.
The arrests of Mr Pelemis and Mr Peric were carried out under the order of Bosnia’s top war crimes court.
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Prosecutors say the two men were commanders in the Bosnian Serb Zvornik brigade, which operated in the Srebrenica region during the war.
They are suspected of taking part in the execution of Muslims in the Srebrenica enclave of Pilica and Branjevo.
Srebrenica was a so-called UN safe haven under the protection of Dutch peacekeepers, but was overrun by Bosnian Serb forces in the late days of the war.
The Srebrenica massacre – Europe’s worst since World War II – has been established as an act of genocide by the UN war crimes tribunal in The Hague.