The 1918 United States Senate election in Mississippi was held on November 3, 1918. Incumbent Democratic U.S. Senator James K. Vardaman ran for re-election to a second term in office, but was defeated in the Democratic primary by U.S. Representative Pat Harrison.

James Kimble Vardaman was an American politician from the U.S. state of Mississippi. A Democrat, he served as the Governor of Mississippi from 1904 to 1908 and then represented Mississippi in the United States Senate from 1913 to 1919.