Chaldean Catholic bishop Antoine Audo said there were about 1.5 million Christians in the country before the start of the conflict in March 2011.
"I think now there are maybe 500,000. Two-thirds have left mainly due to the insecurity," he told reporters in Geneva.
In the embattled northern city of Aleppo, the exodus was even greater, he said, with only around 40,000 of its once 160,000-strong Christian community remaining.
"You cannot imagine the dangers that we face every day," he said.
Wealthy Christians have all left, while "the middle classes have become poor and the poor have become miserable".
But he denied President Bashar al-Assad was to blame for the horrors of the Syria conflict, which has cost more than 270,000 lives in five years.
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"There is no persecution of Christians" by the government, he said.
Rather, they are being "targeted" by jihadists such as the Islamic State group in a bid to "destabilise the Syrian society and transform the war into a confessional war".
Slamming the "propaganda" against Assad, he said he believed 80 percent of Christians in Syria would support him if he stood for reelection, and that overall support would be above 50 percent.
"Even the Sunnis will choose Bashar al-Assad," to ward off the extremists, he said.
Assad's fate is the key issue at peace talks in Geneva, with the main opposition insisting he must go before any transitional government can be agreed, but Damascus saying his removal is "a red line" for negotiations.
The bishop said Syria had long served as a model for how Muslim and Christian communities could live side-by-side and said the hatred on display had been "imported".
"I think... this war is not coming from inside Syria... I think all is organised from outside to destroy Syria."