In 1846 the Board of Foreign Missions appointed the Rev. Matthew R. Miller as its first missionary to the Jews. The Board originally intended to send him to Asia, but these plans did not materialize. Trained in Rabbinical literature and German, Matthew Miller began the mission to the Jews in New York City in 1848. He worked alone until 1849 when he was joined by the Rev. John Neander, a former Rabbi. In 1849, the Rev. Bernard Steinthal was appointed to work among the Jews in Philadelphia, and in 1850 the Rev. Frederick I. Neuhaus among the Jews in Baltimore. In 1853, Mr. Julius Straus, a licentiate preacher, received a temporary appointment to New York. John Neander and Frederick Immanuel Neuhaus were missionaries for the American Society for Meliorating the Condition of the Jews before they came to the Board of Home Missions.

The work eventually dwindled down in 1855 to one missionary, John Neander. Mr. Neander eventually accepted a call to a German church in Brooklyn in 1858, and only gave part of his time to work among the Jews. He continued in this double capacity until 1876, when the Board discontinued its work in the Jewish field. In 1894, mission work to the Jews was transferred form the Board of Foreign Missions to the Board of Home Missions.