Syria’s official news agency SANA reported that Muallem died at dawn on Monday.
According to the report, he would be laid to rest later on Monday in Damascus.
There were no details on the cause of death, but Syria’s top diplomat had for years been in poor health with heart issues.
"He was known for his honorable patriotic positions," the government said in a statement.
According to a source close to the Damascus government, it is widely expected his deputy, Faisal Mekdad, will succeed him as foreign minister.
Muallem first took on the portfolio of the foreign minister in 2006. He was also named as deputy prime minister in 2012.
The veteran diplomat held a succession of top diplomatic posts, including ambassador to the United States.
Muallem’s last statements denounced the persisting and unilateral economic sanctions against the Syrian nation, saying on October 25 that they have deteriorated the economic situation, particularly as the COVID-19 pandemic rages across the globe.
The foreign minister also condemned the Western role in setting conditions and fabricating flimsy pretexts to halt the return of Syrian refugees to their homeland, slamming the West for politicizing the purely humanitarian issue and its use as a card for advancing their political agendas.
Some 5.6 million Syrians have been forced to flee abroad as refugees, mostly to the neighboring countries of Turkey, Lebanon, Jordan, Egypt and Iraq.
Moreover, one million Syrian children have been born as refugees ever since the foreign-backed militancy began in their country back in March 2011.
Syria's top diplomat repeatedly slammed the US role in the conflict that plagued his country.
In August 2012, Muallem said Washington was "the major player against Syria" in the war, noting that the US was supporting terrorism in Syria in spite of its claims to be fighting it.
He also said in his annual address to the United Nations General Assembly in 2019 that "tens of thousands of foreign terrorist fighters have been brought to Syria from more than a hundred countries, with the support and cover of States that are known to all", in an apparent reference to the US and Turkey, who maintain an illegal military presence in northern Syria.