Turkey says Pope Francis' description of the WW1 mass killing of Armenians as genocide shows "the mentality of the Crusades".
The pontiff's remarks have "no relation to reality", Turkish Deputy Prime Minister Nurettin Canikli said.
Armenia and many historians say up to 1.5 million Armenian Christians were killed by Ottoman Turkish forces in 1915.
But Turkey disputes the figure and denies the deaths constituted genocide.
It says the deaths were part of a civil conflict triggered by WW1.
The row continues to sour Turkish-Armenian relations, drawing in other countries such as Germany, whose parliament recently declared the killings to be genocide
Pope Francis made the comments on Friday during a visit to he Armenian capital, Yerevan.
"This tragedy, this genocide, has unfortunately marked the start of a sad series of great catastrophes of the last century," he said.
But Mr Canikli hit back late on Saturday, describing the remarks as "unfortunate".
"It is possible to see all the hallmarks or reflections of the mentality of the Crusades in the Pope's activities," he said, quoted by the state-run Anadolu news agency, referring to military campaigns in Medieval times promoted by the papacy against Muslims in the Middle East.
Pope Francis also used the phrase last year, prompting Turkey to recall its envoy to the Vatican for 10 months.
He ended his visit to Armenia on Sunday with an open-air liturgy and trip to the country's border with Turkey.
War of words
In 2014, for the first time, Turkish Prime Minister Recep Tayyip Erdogan offered condolences to the grandchildren of all the Armenians who lost their lives.
But he also said that it was inadmissible for Armenia to turn the issue "into a matter of political conflict".
Armenia says up to 1.5 million people died in 1915-16 as the Ottoman Empire was disintegrating. Turkey has said the number of deaths was much smaller.
Many of the victims were civilians deported en masse to barren desert regions where they died of starvation and thirst. Thousands also died in massacres.
Most non-Turkish scholars of the events regard them as genocide. Among the other states which formally recognise them as genocide are Argentina, Belgium, Canada, France, Italy, Russia and Uruguay.
Turkey maintains that many of the dead were killed in clashes during WW1, and that ethnic Turks also suffered in the conflict.