The last UN secretary-general to visit Damascus was former UN chief Ban Ki-moon in 2009.
Guterres' visit represents another milestone for Syria since rebels ousted former leader Bashar al-Assad in late 2024, ending the war that began in 2011 and launching a transitional period steered by an Islamist-led leadership.
At the time, Guterres described "the end of the Syrian dictatorship" under Assad as a sign of hope for the region.
Guterres is set to meet President Ahmed al-Sharaa, the former head of al Qaeda's affiliate in Syria who until November 2025 was under terrorism-related sanctions imposed by the UN Security Council.
The UN chief will also meet Syrian Foreign Minister Asaad al-Shaibani, other government officials and representatives of Syrian civil society, UN spokesperson Stephane Dujarric said.
Guterres will underline that the country has an opportunity "not only to recover from conflict, but also to lay the foundations for a future for Syria that will be more stable, more inclusive, and more prosperous for all Syrians," Dujarric said.
Guterres is expected to be in Damascus for several days, but the full schedule of his visit has not been released by his office.
He is visiting just weeks after two bombs exploded near a hotel in Damascus where French President Emmanuel Macron spent the night, overshadowing the first visit to Syria by a European Union head of state since Assad was toppled.
Sharaa's government is seeking to rebuild Syria's international ties and economy after nearly 14 years of war and decades of isolation under Assad family rule.
The transition has been marred by two major episodes of sectarian bloodshed that have tested Sharaa's repeated pledges to protect Syria's religious minorities.
Nearly 1500 Alawites - the sect that Assad was from - were killed in Syria's coastal region last year by government-aligned factions, and hundreds of Syrians from the Druze minority were killed months later in the country's south.
Guterres expressed alarm over both bouts of violence and has called for accountability.
Sharaa, who broke ties with al-Qaeda in 2016, led an alliance of Islamist rebel factions that ousted Assad in a lightning offensive in December 2024.
Since taking power, his government has sought to re-establish Syria's diplomatic ties to expand beyond Assad's longtime allies, Russia and Iran.
Last year, Sharaa became the first Syrian president since 1967 to take part in the UN General Assembly in New York.
The United States has lifted most sweeping sanctions on Syria and U.S. President Donald Trump informed Sharaa earlier this month that he intended to remove Syria from Washington's list of state sponsors of terrorism.
Guterres is expected to address Syria's new parliament on Monday and will visit a UN peacekeeping force that has maintained a buffer zone between Israeli and Syrian forces for decades, Dujarric said.
