He played college football for the TCU Horned Frogs, where he won the Heisman Trophy[1] and the Maxwell Award in 1938, the first quarterback to win either.

[3] O'Brien played college football at nearby TCU in Fort Worth in 1935 as a backup for Sammy Baugh.

[5] He was selected by the Philadelphia Eagles, and owner Bert Bell gave him a $12,000 bonus and a two-year contract, and he signed with the team in March.

[7] After two seasons with the Eagles, O'Brien retired from football to become an agent in the Federal Bureau of Investigation (FBI),[10] where he worked for ten years.

O'Brien later entered the oil business, working for Dresser Atlas Industries of Dallas[3] and was an adviser to Lamar Hunt during the founding of the American Football League.

[12] O'Brien was also president of the TCU Alumni Association, a YMCA board member, a chair of the Tarrant County Democratic Party, a supporter of Golden Gloves youth boxing programs, and a deacon of University Christian Church.

In 1971, O'Brien was diagnosed with cancer and underwent surgery to remove a kidney and part of his right lung, but eventually died from the disease on November 18, 1977.