The air attack on the night of June 7 to 8 targeted the village of Zardana in Idlib province and left 44 dead including six children, according to the British-based Syrian Observatory for Human Rights.
In a statement, Guterres expressed "deep concern" about the strikes and called for a "full investigation into the attacks, especially allegations that there was also a second strike targeting first responders, to establish accountability."
He recalled that Idlib is part of the de-escalation agreement for Syria reached between Turkey, Russia and Iran and urged those guarantors to uphold their commitment.
Most of Idlib province is held by an array of Islamist and jihadist groups with only parts controlled by the Russian-backed government.
Since Russia intervened in its support in 2015, the government has regained control of around half of the country.
More than 350,000 people have been killed in the Syrian war since it started in 2011 with the brutal repression of anti-government protests.