The collection consists of 350 titles from the personal library of the philosopher and man of letters, George Santayana (1863-1952). The subject focus of this portion of Santayana's library, purchased by the University of Waterloo Library during the 1960's, could be characterized as interdisciplinary, with works in philosophy, literature, religion, and history. Many of the books were presented to Santayana by their authors. The collection is supplemented by reference and critical materials related to the life and work of Santayana as well as editions of Santayana's own writings. First or early editions of most of Santayana's works are included.

One of the most interesting and significant features of the Library of George Santayana is that many of the books from his personal library contain annotations in his own handwriting. These notes reveal his opinions and thoughts about the writings of others. The collection includes Santayana's own copies of his three-volume autobiography, with his corrections and notes to his publisher.