St. Ambrose College was established in 1882 by Bishop John McMullen. The first library collection was made up of books donated by the early priest faculty members.The first Library was housed on the third floor of the center portion of the current Ambrose Hall. According to the 1903 catalog, the library held 4,000 books.
In 1927 the Library collection was moved to the Davis Hall basement, where it remained until 1941. By then, the collection had grown to 15,000 volumes.
On October 24, 1941 a new Library/Administration building was dedicated in what is now McMullen Hall. In 1978-79 the administrative offices were moved to Ambrose Hall. From that point in time, the building housed Library services and a small computer lab until the Library moved to a new building in the spring of 1996. On September 19,1982, during the centennial year of the college, the Library was rededicated and named in honor of Bishop John McMullen, the founder of the college. During the Library's fifty-five years in this building, the collection grew from the original 15,000 located in Davis Hall to about 115,000 books and 40,000 bound journals.
On March 18, 1996, the Library began services from the new building, a 58,000 square foot, $8.5 million dollar facility incorporating the latest hi-tech capabilities. The Library has seating for 400 users, plus group and individual study rooms. The shelving capacity is 250,000 volumes.
On Sunday, October 6, 1996 the Library was dedicated by the current Bishop, William Franklin and named for retired Bishop Gerald F. O'Keefe. The keynote address was presented by Mary Dempsey, Library Commissioner for the Chicago Public Library. In August 2007, the Board of Directors voted to change the name of the Library to the St. Ambrose University Library.