Addressing the congregation of the St Yeghiche Armenian Church in South Kensington, London, the Prince of Wales said that the faith was "quite literally, grotesquely and barbarously assaulted".
He said: "We must all as Christians seek to do. For some time now I have been troubled by the appalling atrocities faced by Christians suffering in the Middle East...It is the most soul destroying tragedy."
Armenian Christians have been targeted in the Syrian civil war and also suffered elsewhere.
The Prince added that the group has long lived peacefully with their neighbours.
He said: "It is heartbreaking to learn of the attacks on Christians and on Churches where they gather, such as the Church in Deir el Zour (Syria) earlier this year."
Charles went on to express his sympathies for those suffering as a result of ongoing attacks, adding: "They seem so hopelessly inadequate but please, please just know truly heart felt they are."
Avak Asadourian, the Archbishop of Iraq, spoke during to service of the problems facing Armenian Christians, particularly that the of the so-called Islamic State militant group (also known as Isis or Isil).Speaking from his own experience, he said: "Due to assaults Iraqi Christians are leaving the country of their forefathers. In 1980 there were 1.5 million, this is now down to 400,000 due to the encroachment of Isis.
"If political measures are not adopted very soon, then in the Middle East Christian manifestations will cease to exist in its own birthplace."
Charles also spoke with Bishop Vahan Hovhanessian, Primate of the Armenian Church in the UK, and doctor Armen Sarkissian, the Armenian ambassador.
The Prince has existing ties with the Armenian community after visiting the country in May 2013.
While there he spoke with some of the country's leading Christian figures, and has expressed an interest in encouraging an inter-faith dialogue.
Charles also showed concern over the plight of Christians in some Middle-Eastern nations during a visit to the Coptic Orthodox Church Centre in Stevenage and the Syrian Orthodox Church in Acton last year.