The pontiff's remarks have "no relation to reality," Turkish Deputy Prime Minister Nurettin Canikli said, the BBC wrote.
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 the 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.
Read alsoGerman MPs recognize Armenian 'genocide' amid Turkish fury – BBCPope 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.