Russia and Turkey launched the patrols along the M4 highway in March following a ceasefire agreement aimed at stopping heavy fighting in and around Idlib, the last major bastion of anti-government forces in Syria's civil war.
The device blew up at 8:50 local time (05:50 GMT) as their convoy patrolled the M4 in the southern part of a de-escalation zone, a statement said.
A Russian and a Turkish armoured vehicle were damaged, with three Russians "lightly injured", it said. Several Turkish soldiers were also wounded.
Russia backs Syrian President Bashar Assad in the conflict and Turkey backs the opposition, but the two countries have agreed several deals to reduce hostilities.
Rami Abdel Rahman, the director of the Britain-based Syrian Observatory for Human Rights, reported that "numerous explosions were heard as the patrol passed in a village northeast of the town of Ariha".
The blast occurred "despite Turkish forces having heavily combed the area 24 hours before the joint patrol set off on the road separating areas controlled by the rebels from those held by government forces, according to the ceasefire".
No such patrols had yet been able to circulate along the entire length of the road as stipulated in the ceasefire agreement, from the village of Tarbana in the east of Idlib province to the village of Ain Hawr in the north of Latakia province, the observatory said.
Extremists opposed to the patrols as well as protests against them had previously prevented them from advancing, but without them ever being targeted like this, it said.
A little-known t group known as Kataib Khattab Al Shishani claimed responsibility on its Telegram channel which was created only one month ago.
"This [attack] was just a warning, what is coming is worse," it said.
It was not immediately clear who the group is affiliated to and AFP could not independently verify the authenticity of the claim.
Home to some 3 million people, Idlib region is dominated by the Hayat Tahrir Al Sham group, an extremist outfit let by ex-leaders of Syria's former Al Qaeda affiliate, and its rebel allies.
A Russian-backed government offensive displaced nearly a million people between December and March, but thousands have returned since the truce came into force.
After Tuesday's attack, Russian warplanes launched several air strikes on militants’ positions in the countryside of Latakia province, said the observatory.
They also pounded areas in southern Idlib in tandem with government artillery attacks which wounded some five people in the Idlib town of Ariha.
Syria's nine-year-old war has killed more than 380,000 people and displaced nearly half of the country's pre-war population.