The 1922 United States Senate election in Wyoming took place on November 7, 1922. First-term Democratic Senator John B. Kendrick ran for re-election to a second term. He was opposed by Republican Congressman Frank W. Mondell, the Majority Leader of the U.S. House of Representatives. Kendrick won re-election by a wide margin, defeating Mondell, despite his long record of representing the state in Congress, with 57% of the vote to Mondell's 43%. Kendrick was also able to increase his margin of victory from 1916, despite Republicans generally doing well in Wyoming in 1922.
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