All four men, who were transferred in May from the UN war crimes tribunal in The Hague, denied the charges.
Mejakic was the guard commander and Gruban was a guard shift commander at Omarska where 3,000 Muslims and Croats were kept in inhumane conditions and subjected to physical, psychological and sexual maltreatment, according to the charges.
Fustar was a guard shift commander at Keraterm where 1,500 non-Serbs were detained and where hundreds of detainees were believed to have been killed.
Knezevic had no official position in either of the two camps but was charged with killings and beatings in both places.
The international tribunal in The Hague has tried 10 Bosnian Serbs for crimes committed in the Prijedor area and gave them jail terms ranging from five to 40 years. One indicted man remains at large.
Almost 2,300 Muslim, Croat and other non-Serb victims from the Prijedor area have been exhumed from 53 mass graves and several hundred individual graves so far, while 1,100 are still unaccounted for.
Wednesday's trial was the third case transferred to Bosnia's new war crimes court from the UN tribunal as part of its strategy to send low- and mid-level cases to countries in the region as it prepares to shut down its operations by 2010.