"The Ministry of Foreign Affairs and Expatriates mourns the death of Deputy Prime Minister and Minister of Foreign Affairs and Expatriates Walid Muallem," a statement by the Syrian Foreign Ministry said on Monday.
There were no details on the cause of his death, but the 79-year old had for years been in poor health with heart problems.
Al-Muallem worked at the Syrian Foreign Ministry since 1964. He served in Syrian diplomatic missions in Tanzania, Saudi Arabia, Spain, the UK, was the ambassador to Romania and the US.
The veteran diplomat was first appointed foreign minister in 2006 and also held the post of deputy prime minister.
He was a close ally of President Bashar al-Assad during the country's civil war, which erupted in 2011.