The 1946 United States Senate election in Wyoming took place on November 5, 1946. Democratic senator Joseph C. O'Mahoney ran for re-election to a third term. In the general election, he faced Republican Harry B. Henderson, the former chairman of the Republican Party of Wyoming and a former state senator. Despite the strong performance of the Republican Party nationally, O'Mahoney's popularity was strong enough for him to win re-election yet again by a wide margin, though slightly narrower than his 1940 re-election.