In 1968, he graduated with a bachelor's degree in chemical engineering from , from which he also received an honorary doctor of science degree in June 2002.
He began his career with Chevron Research Co. as a process engineer in 1968. On January 1, 2000, he became chairman and CEO of Chevron, succeeding Kenneth T. Derr. He retired effective December 31, 2009.
In January 2010, O'Reilly joined the Board of engineering and construction giant, Bechtel Corporation. In August 2010, he was appointed a director on the board of Saudi Aramco, the national oil company of Saudi Arabia. He also is vice chairman of the National Petroleum Council.
O'Reilly also serves on the San Francisco Symphony Board of Governors. In April 2002, O'Reilly received the from Kazakhstan president Nursultan Nazarbaev.
He is a member of The Business Council, J. P. Morgan International Council, the World Economic Forum’s International Business Council, and the American Society of Corporate Executives.
Married Janet Patricia Whelpdale, March 10, 1973. Children: A. Luke, Alice.