Father Thomas Cooke Middleton was born in Chestnut Hill, Pennsylvania, on 30 March 1842 of a Quaker family. He was baptized at the age of 12 with his entire family, then including his mother and five sisters. He entered the Augustinian novitiate at Tolentine, Italy, in 1858, and was ordained to the priesthood in 1864.

In 1865, Father Middleton returned to the United States and Villanova College, where he served and lived for the next 58 years. At Villanova College he was a teacher, Prefect of Studies of the College, Archivist, and Secretary and Socius of the Province. He also served as President of Villanova College from 1876 to 1878 and College Librarian from 1865 to 1923.

In 1884, Father Middleton helped organize the American Catholic Historical Society of Philadelphia, of which he was the first President. He was the author of many essays on local Catholic history and the history of the Order of Saint Augustine, including the Introduction to the Oratorian translations of the Life of Saint Thomas of Villanova. He also prepared an historical sketch of Villanova College (Historical Sketch of the Augustinian Monastery, College, and Mission of St. Thomas of Villanova, Delaware County, Pa: During the first half century of their existence, 1842-1892 (Villanova, Pa., 1893)) which was published on its fiftieth anniversary in 1893.

Father Middleton was 81 when he died at Villanova on 19 November 1923. He is buried here at Villanova in the Augustinian Community Cemetery. Middleton Hall, the Health Center at Villanova University, is named in his honor.