Born in County Cork, Ireland, O’Reilly moved to San Francisco, California with his family six weeks after he was born. He has two brothers and three sisters.

O’Reilly was initially interested in literature upon entering college. He graduated from Harvard College in 1975 with a B.A. cum laude in Classics, and married his wife, Christina, an elementary school teacher. They moved to the Boston area, and in 1977, he began publishing computer user manuals. He defines his company not as a book or online publisher, nor as a conference producer (though the company does all three), but as a technology transfer company, “changing the world by spreading the knowledge of innovators.”

O’Reilly serves on the board of directors of three companies, Safari Books Online, Maker Media, and PeerJ. He served on the board of Macromedia until its 2005 merger with Adobe Systems, and on the board of MySQL AB until its sale to Sun Microsystems. He also serves on the board of directors for the public-service organization Code for America. In February 2012, he joined the UC Berkeley School of Information Advisory Board.

O’Reilly was also a friend of science fiction writer Frank Herbert, and published a critical study of Herbert’s work, Frank Herbert in 1981. O’Reilly also edited a collection of Herbert’s essays and interviews, The Maker of Dune: Insights of a Science Fiction Master.