He founded the stock brokerage firm William O'Neil & Co. Inc in 1963 and the financial newspaper Investor's Business Daily in 1984.

[3] He studied business at Southern Methodist University, received a bachelor's degree in 1955 and served in the United States Air Force.

[4] In 1958, O'Neil started his career as a stockbroker at Hayden, Stone & Company, and developed an investment strategy which made early use of computers.

[16] In 1984, O'Neil made research from his database available in print form with the launch of Investor's Daily, a national business newspaper aimed to compete with The Wall Street Journal.

He stated in a 2002 interview that one of the books which was an early influence on him was Gerald Loeb's The Battle for Investment Survival.

[22] In 2007, O'Neil started donating to his alma mater, Southern Methodist University and funded a chair in business journalism at SMU's Meadows School of the Arts.