From the beginning of the 19th century, Christian missionary groups began to seen in the Ottoman territory. The most active of these groups was American Protestant missionaries. When they set foot on the Ottoman land, so to speak, the seeds of Protestantism were laid by the pioneers of the American Board of Commissioners for Foreign Missions, which was one of the America's most important missionary congregations. Abbreviated as ABCFM or BOARD, it was among the most influential and leading missionary organizations in America. Board missionaries, following their tours throughout Anatolia, determined their main fields of activity and concentrated all their activities on Gregorian Armenians. As a result of their endeavour, a Protestant Armenian community was formed within the Ottoman society in a fairly short period of time. Especially on the occasion of the pressure of the British and Americans, this congregation was officially recognized with an edict granted by Abdulmecid in 1850. Antep was one of the cities, the Board organization placed a particular importance, which engaged in establishing schools, churches and hospitals in various places of the Ottoman lands. The missionaries who designated Antep as the missionary centre and worked in intensively there, established school, college and hospital. The activities of missionaries in Antep made it to be recognized as an exemplary centre for missionaries. The main aim of this study is to evaluate the initial stage of Protestant missionaries in Antep through Board reports, primary sources and related literature, and thus to contribute to the understanding of organization method of the American Board in the Ottoman geography.