At the end of the First World War, a profoundly transformed Middle East faced massive population displacements and health crises, which presented crucial challenges for humanitarian actors. North American philanthropy and charity played a decisive role in this context. Among the organisations involved, the Catholic Near East Welfare Association (cnewa) is not well known. It was established by American Catholics to help Eastern Christians – especially Greek Catholics – and to thwart the influence of Protestantism in the region, mainly by supporting local Churches and missions in their humanitarian and welfare work. cnewa was quickly placed under the supervision of the US episcopate and the Vatican, partly transforming its operations and purposes. Its activity became closely involved with the Eastern policy of the Holy See, which primarily focused on the “return” of Orthodox Christians to the Roman Church. This article, at the crossroads of the history of mission and humanitarian aid, examines the early developments of cnewa and highlights how the Catholic Church dealt with the emergence of modern humanitarian aid in the mid-twentieth century.