The attack, launched by gunmen, targeted three passenger vehicles on Thursday, reportedly killing at least 42 people and injuring 20 others, Xinhua reported.
The secretary-general stressed that attacks against civilians are unacceptable, said Stephane Dujarric, his spokesman, at a daily briefing.
Guterres extended his deepest condolences to the families of the victims and the government of Pakistan.
He called on the Pakistani government to conduct an investigation and to ensure that those responsible are held accountable.