Foreign ministry spokesman Ramin Mehmanparast condemned the "tragic incident" and expressed sympathy with the families of the victims, the state broadcaster's website IRIB reported.
He also called on American society to mobilise against "warmongering and the massacre of innocent people anywhere, through terrorism, whether state-sponsored or not."
"There is no difference between children and teenagers who fall victim to armed actions, whether it be inside Gaza, the US, Afghanistan, Pakistan, Iraq or Syria," Mehmanparast said in a statement.
The massacre on Friday inside the school in Newtown, Connecticut has provoked shock and sympathy around the globe.
Iran and the United States have had no diplomatic relations for over three decades. The two arch-foes regularly accuse each other of supporting terrorist groups in the Middle East.