In 1849, he entered the Lutheran ministry and became pastor at Delaware, Ohio. In 1865 he resigned his pastorate to become professor in the Theological Seminary of Capital University, Columbus, Ohio. In 1881 he was elected president of Capital University. Following a critical attack of angina pectoris, he retired as professor emeritus in 1902.
Loy edited the official periodical of the Evangelical Lutheran Joint Synod of Ohio, the Lutheran Standard, from 1864 until 1890. In 1881, he founded the Columbus Theological Magazine and managed it for ten years. He was President of the Ohio Synod from 1860 to 1878 and again from 1880 to 1894. In 1887, Muhlenberg College gave him the degree of Doctor of Divinity. He wrote twentyone hymns and also translated a number of German hymns into English. He also edited a translation of Luther's House Postil (3 vols., 1874–1884).
The Americanization process in the second generation; the German Lutheran Matthias Loy (1828-1915) caught between adaptation and repristinization. (Studies in religious leadership; v.2) by C. George Fry and Joel R. Kurz, (2005), ISBN 0-7734-6156-6