Born of Orthodox Jewish parents in a Lithuanian village, Schereschewsky early showed gifts for religious leadership and was trained for the rabbinate, with graduate studies in Germany. During these years he was drawn to a serious consideration of the Christian faith through contact with missionaries of the London Society for Promoting Christianity amongst the Jews. In 1854 he immigrated to America, and through contact with Jewish Christians, felt called to become a Christian in fulfillment of his Hebrew heritage. His gifts for leadership were immediately recognized and he was sent to Western Theological Seminary in Pittsburgh, Pennsylvania. The issue of catholicity intrigued him eventually led him to transfer to General Theological Seminary in New York City as preparation for ordination in the Episcopal Church.
Hearing the call for missionaries for China, he left for Shanghai in 1859 and began his study of Chinese during the voyage. A gifted linguist, he translated the Bible and the Church of England Prayer Book into Mandarin. His scholarship was matched by his love for people. He was elected bishop of Shanghai in 1877, and he was consecrated in Grace Church, New York City. He helped establish St. John's College (later University) in Shanghai. He resigned his see in 1883 when he became stricken with paralysis. After treatment in the West, he returned to Shanghai in 1895 to continue his translation work. He typed some 2,000 pages with the middle finger of his partially crippled hand. While the paralysis seemed a terrible affliction, he came to believe that God guided his life so that he could do the work for which he was best fitted. His wife was his constant companion and source of help until he died in Tokyo. He is remembered in the Episcopal book Lesser Feasts and Fasts on October 15.