Employees who worked on the illegal transactions must not work with the bank again, the Federal Reserve said.
The bank also violated various New York state laws and is paying the two agencies separately.
"The firm did not have sufficient policies and procedures to ensure that activities conducted at its offices outside of the United States complied with US sanctions laws," an official from the Federal Reserve said.
The Federal Reserve is requiring Deutsche Bank to create an "enhanced" programme to "ensure global compliance" with US sanctions, characterising its transactions with Syria and Iran "unsafe and unsound".
The bank said in a statement that the conduct had stopped several years ago, adding: "Since then we have terminated all business with parties from the countries involved."
Two French banks, BNP Paribas and Credit Agricole, received higher fines from the US for working with US-sanctioned countries.
The US fined BNP Paribas $8.9bn (£5.8bn) and fined Credit Agricole $800m (£516m).
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