[5][6] Its first published book was Robert F. Harper's Assyrian and Babylonian Letters Belonging to the Kouyunjik Collections of the British Museum.

For its first three years, the press was an entity discrete from the university; it was operated by the Boston publishing house D. C. Heath in conjunction with the Chicago printer R. R. Donnelley.

Composed of articles and monographs by scholars and administrators on the state of the university and its faculty's research, the Decennial Publications was a radical reorganization of the press.

Leading books of that era include Edgar J. Goodspeed's The New Testament: An American Translation (the press's first nationally successful title) and its successor, Goodspeed and J. M. Povis Smith's The Complete Bible: An American Translation; Sir William Alexander Craigie's A Dictionary of American English on Historical Principles, published in four volumes in 1943; John Manly and Edith Rickert's The Canterbury Tales, published in 1940; and Kate Turabian's A Manual for Writers of Term Papers, Theses, and Dissertations.

Of the press's best-known books, most date from the 1950s, including translations of the Complete Greek Tragedies and Richmond Lattimore's The Iliad of Homer.

That decade also saw the first edition of A Greek-English Lexicon of the New Testament and Other Early Christian Literature, which has since been used by students of Biblical Greek worldwide.

The press has recently expanded its digital offerings to include most newly published books as well as key backlist titles.

University of Chicago Press joined The Association of American Publishers trade organization in the Hachette v. Internet Archive lawsuit which resulted in the removal of access to over 500,000 books from global readers.

[12][13] The Journals Division of the University of Chicago Press publishes and distributes influential scholarly publications on behalf of learned and professional societies and associations, foundations, museums, and other not-for-profit organizations.

[14] All are peer-reviewed journals of original scholarship, with readerships that include scholars, scientists, and medical practitioners as well as interested, educated laypeople.

In 2009, the CDC enabled the sales of electronic books directly to individuals and provided digital delivery services for the University of Michigan Press among others.