Jihadists destroyed the Nabi Shiyt (Prophet Seth) shrine in Mosul, the de facto Iraqi capital of the "caliphate" proclaimed last month by Islamic State (IS) leader Abu Bakr al-Baghdadi.
"IS militants stopped people from coming close, set explosives in and around the shrine and then detonated them as a crowd looked on," one resident who witnessed the demolition told AFP.
Seth is revered in Christianity, Islam and Judaism as the third son of Adam and Eve.
"These people follow this impossible religious doctrine according to which they must destroy or kill anything or anybody deviating from their views," he said.
"That simply has nothing to do with Islam."
The latest destruction comes a day after IS militants completely levelled the reputed tomb of Jonah (Nabi Yunus) in Mosul, sparking an outcry among religious officials.
"This most recent outrage is yet another demonstration of the terrorist group's intention to shatter Iraq's shared heritage and identity," the top UN envoy in Iraq, Nickolay Mladenov, said.
"He was a prophet for all religions," Sadr said in a statement, adding that the perpetrators of the desecration "don't deserve to live".
Sunni and Shiite religious officials have said IS militants had destroyed or damaged dozens of shrines and husseiniyas in and around Mosul since they overran part of the country six weeks ago.
Husseiniyas are Shiite places of worship that are also used as community centres.
