"After the arrest of two people suspected of spying for Syria, I have decided to expel four members of the Syrian embassy in Berlin," Westerwelle said in a statement.
"The Syrian ambassador has been informed of this decision," added the minister.
According to diplomatic sources, there were "clear indications" that the four had carried out "acts not in accordance with diplomatic law."
The diplomats and their families now have three days to leave the country, the sources added.
Further steps against Syrian embassy staff could not be ruled out if it emerged that the Damascus regime was continuing to interfere with opposition figures and Syrian people in Germany, added the sources.
Two men, identified only as 47-year-old German-Lebanese citizen Mahmoud El A. and 34-year-old Syrian national Akram O., were arrested in Berlin on Tuesday.
Westerwelle summoned Syria's ambassador following the arrests.
"The position of the federal government was made unmistakably clear at this meeting that the possible action against the Syrian opposition in Germany will not be tolerated," the German Foreign Ministry said.
In late December, a Berlin local politician active in the Syrian opposition was attacked by two men in his home in a case the Foreign Ministry said it was following closely.
The man's party, the Greens, said it suspected the Syrian secret services were behind the assault.
No suspects have been identified in the case.