After three years out of politics, Coburn announced his candidacy for the Senate seat being vacated by four-term incumbent  Republican Don Nickles. Former Oklahoma City Mayor Kirk Humphreys (the favorite of the state and national Republican establishment) and Corporation Commissioner Bob Anthony joined the field before Coburn. However, Coburn won the primary by an unexpectedly large margin, taking 61% of the vote to Humphreys's 25%. In the general election, he faced Brad Carson, the Democrat who had succeeded him in the 2nd District and was giving up his seat after only two terms.