While B. Carroll Reece was the Chairman of the Republican National Committee (RNC), Republican leaders in Tennessee began to discuss the prospect of Reece running for the United States Senate. As Tennessee law allowed a person to qualify for a primary without candidate consent, Reece's associates entered his name into the primary. Reece stepped down from his chairmanship of the RNC after the nomination of Thomas E. Dewey at the 1948 Republican National Convention. After considering the option of running for his former position representing Tennessee's 1st congressional district, Reece instead announced his candidacy for the Republican nomination for the United States Senate.[4] Allen J. Strawbridge, a lawyer from Dresden, Tennessee, was also certified to participate in the Republican primary.[5] Reece defeated Strawbridge in the Republican primary.[3]
In the general election, Reece ran on an anti-communist platform.[4] An uncertainty at the beginning of the general election was Boss Crump. Kefauver had won over Crump's preferred candidate and Crump had long maintained a political détente with East Tennessee Republicans. Tennessee Republicans were optimistic that Crump would either support Reece or oppose Kefauver. While Crump did not support Kefauver, he did drop his opposition in the month before the election. Reece lost the general election by a similar margin as most Tennessee Republicans running statewide in that era.[4]