Germany detained the two men earlier this year under its "universal jurisdiction" laws that allow it to prosecute people for crimes against humanity committed anywhere in the world.
Prosecutors said charges against the main suspect, identified as Anwar R. under Germany's privacy rules, include 58 murders and multiple sexual assaults in a Damascus prison where at least 4,000 opposition activists were tortured.
It said 56-year-old Anwar R. oversaw interrogations at the facility and is suspected of involvement in crimes against humanity between 2011 and 2012. He left Syria in 2012 and arrived in Germany in July 2014.
The second suspect, Eyad A., is charged with facilitating the torture of at least 30 opposition activists arrested after intelligence agents opened fire on an anti-Assad demonstration in Douma near Damascus in Autumn of 2011.
Eyad A., who left Syria in 2013 and arrived in Germany in April 2018, worked for an intelligence unit led by Anwar R. Both suspects had applied for asylum in Germany.
"Eyad A. knew before the arrest of demonstrators of the systematic and brutal torture methods practiced at the facility," the Federal Prosecutor's Office (GBA) said in a statement.
No date was set for a trial and no comment was available from the two Syrians.
Efforts to prosecute members of Assad’s government have repeatedly failed, as Syria is not a signatory to the Rome Statute of the International Criminal Court in The Hague. Russia and China have also vetoed attempts to give the ICC a mandate to set up a special tribunal for Syria.
But human rights lawyers in Europe have been collecting testimonies from survivors among the hundreds of thousand of Syrians who have sought refuge, mainly in Germany and Sweden, to prosecute members of Assad's government.
German prosecutors last year issued an international arrest warrant for the head of Syrian Air force Intelligence on charges of war crimes and crimes against humanity.Syrian human rights lawyers in Germany say their goal is to collect enough evidence from survivors of torture and sexual violence, as well as from the families of victims to convince German prosecutors to issue an arrest warrant for Assad.