David and Catherine Talmage's twelfth child, Thomas Dewitt, was born January 7, 1832, in Gatesville, New Jersey. Talmage was raised in a Christian home, accustomed to daily prayers and Bible readings led by his parents. He entered New York University to study law at age eighteen, the same year he was converted. After three years at NYU he entered New Brunswick Theological Seminary, completing the requirements for his B.D. in 1856. In 1884 he received an honorary doctorate from the University of Tennessee.

Talmage's first pastorate was at the Reformed Church in Belleville, New Jersey. While there he married Mary Avery of Brooklyn with whom he had two children, Thomas and Jessie. Pastorates followed at the Second Reformed Church of Syracuse, New York (1859), and the Second Reformed Church of Philadelphia, Pennsylvania (1862). Shortly after arriving in Philadelphia, his wife drowned in a boating accident. On May 7, 1863, Talmage married Susan C. Wittenmore. The couple had five children: May, Edith, Frank, Maud, and Daisy.

While in Philadelphia Talmage worked as a chaplain in the Union army. He also began a lecture series in addition to his preaching ministry. The income from the lectures allowed him to travel extensively in the U.S. and abroad.

In 1869 he moved to Brooklyn, New York, to pastor the Central Presbyterian Church. An attempt to slander Talmage's work backfired as journalists attending his services to hear backlashes instead printed his sermons. Soon Talmage's sermons began to appear in publications all over the country. It is estimated that over thirty million people read his articles.

Talmage experienced great success in his Brooklyn ministry. The congregation outgrew its facilities so the preacher designed and built the Brooklyn Tabernacle. Talmage saw the building burn to the ground three times and rebuilt the structure twice.

Other activities engaged Talmage's interest such as the founding of the Free Lay College in Brooklyn. He also served as president of the institution. Several magazines enjoyed his editorship: Christian at Work (1873-1976), Advance (1877-1878), Sunday Magazine (1879-1889), and Christian Herald (1890-?).

Susan Talmage died in 1895 just prior to Talmage's moving to the first Presbyterian Church of Washington, D.C. as co-pastor. Mrs. Charles Collier, a widow, married Talmage in January 1898 accompanying him on several tours to Europe, Mexico, and the western part of the United States. While in Mexico during March 1902, Talmage became ill. His condition worsened all the way returning to Washington. He died on April 12 and was buried in Greenwood Cemetery, Brooklyn, New York.