Conference play began with a loss in the annual Red River Rivalry to the Texas Longhorns on October 8, and ended with a win at home in the annual Bedlam Series over the Oklahoma State Cowboys on November 26.

The Sooners finished the regular season with a 7–4 record (6–2 in the Big 12), their worst record since 1999, finishing in a tie with Texas Tech for second in the Big 12 South.

Following the season, Davin Joseph was selected 23rd overall in the 2006 NFL draft, along with Chris Chester in the 2nd round, Dusty Dvoracek, Travis Wilson and Clint Ingram in the 3rd, and J. D. Runnels in the 6th.

Quinn receiving money from a car dealership for work they did not perform.

The following Oklahoma players were either selected or signed as undrafted free agents following the draft.