The extremists blew up an Assyrian parish in the north-eastern village of Tel Nasri.
The Yoldath Aloho Church [Church of the Virgin Mary] was badly damaged in the explosion.
It's thought the building was being used as a headquarters for IS which had taken control of the village on March 7.
The Assyrian Network for Human Rights reports the terrorists detonated the explosives as Syrian and Kurdish forces attempted to enter the village to take it back.
A number of terrorists and soldiers are thought to have been killed.
Human rights groups in Syria have said it is a 'war crime'.
The Assyrian Network for Human Rights said: "[We] condemn the targeting of the Church of the Virgin Mary by [IS] as a war crime under international humanitarian law, which prohibits the targeting of religious buildings during armed conflict."
Yesterday during his Easter Sunday message Pope Francis urged the world not to 'stand by' whilst Christians were targeted in Iraq and Syria.
He said: "We ask for peace, above all, for Syria and Iraq, that the roar of arms may cease and that peaceful relations may be restored among the various groups which make up those beloved countries.
"May the international community not stand by before the immense humanitarian tragedy unfolding in these countries and the drama of the numerous refugees.
"From the risen Lord we ask the grace not to succumb to the pride which fuels violence and war, but to have the humble courage of pardon and peace.
"We ask Jesus, the Victor over death, to lighten the sufferings of our many brothers and sisters who are persecuted for his name, and of all those who suffer injustice as a result of ongoing conflicts and violence."
(Image shows church before explosion.)