The arrests were made in the Gothenburg area on Thursday morning, a spokesperson for Sweden's Security Service (Säkerhetspolisen or Säpo) told Swedish news agency TT.
Prosecutor Ronnie Jacobsson confirmed that the suspects were being held over offences alleged to have taken place in Syria two years ago.
"The men are 30 and 32, Swedish citizens and residents in Gothenburg," he said.
"Both are suspected of a terrorist homicide in Syria in the spring of 2013," he added.
"There may be more people that we need to talk to, so I can say no more at the moment."
Säpo, west Sweden's regional police force and the country's National Task Force (Nationella insatsstyrkan) took part in an operation to arrest the suspects on Thursday morning.
"It is the first time in Sweden that people have been arrested in an investigation into terrorist crimes in Syria," a press officer for Säpo, Sirpa Franzén, told the AFP news agency.
However, she added that the investigation was at a "sensitive stage" which meant that little information could be revealed about the case.
At least 150 Swedish residents are known to have gone to Syria or Iraq to fight for Isis or other extremist groups, according to Sweden's security service Säpo, with intelligence suggesting that at least 35 have been killed.
“We will put forward proposals in parliament in autumn with suggestions for criminalizing the acts of organizing, recruiting and financing terror trips. Participating at training camps for terrorism, for example, is not punishable today,” Interior Minister Anders Ygeman told TT on Thursday.
More than 215,000 people have died in Syria's four-year war, which is increasingly dominated by violent jihadist groups such as Isis, who want to rid the country of western influence and build a state based on radical Islamist ideology.