Wyoming was won by incumbent Democratic President Harry S. Truman, running with Senate Majority Leader Alben W. Barkley, with 51.62 percent of the popular vote, against the Republican nominee, 47th Governor of New York Thomas E. Dewey, running with California Governor and future Chief Justice of the United States Earl Warren, with 47.27 percent of the popular vote, despite the fact that Dewey had previously won the state four years earlier.

Dewey ran a low risk campaign, largely avoiding criticizing Truman, which was due to many believing his hawkish campaign 4 years earlier had cost him the election to Truman's Democratic predecessor, Franklin D. Roosevelt.

Truman suffered from low approval ratings and dealt with many southern Democratic voters defecting to the Dixiecrat candidate Strom Thurmond, costing him the traditionally Democratic strongholds of South Carolina, Alabama, Mississippi, and Louisiana, however Truman's unexpected strength in the Midwest and West Coast secured his reelection, as he flipped the states of Ohio, Iowa, Wisconsin, Colorado, and Wyoming, all of which had voted for Dewey in 1944.

Truman was popular among rural voters, and with agriculture being one of the biggest parts of Wyoming's economy, Truman's support for New Deal era programs that attempted to provide relief to farmers, which along with The Civilian Conservation Corps program greatly impacted Wyoming, allowing new National Parks to be built in the state, was popular among Wyoming voters, and he successfully painted Dewey as more conservative than he was, ignoring the fact that he was significantly more liberal and supportive of New Deal programs like Social Security than many of the conservative Congressional Republicans such as Senator Robert A. Taft from Ohio.

This change was reflected in Wyoming, as the state's Class II Senate seat would flip into Democratic hands with Lester Hunt's landslide victory, who outperformed the top of the ticket by 9.9%.