Because no candidate gained a simple majority of the vote, a runoff between the top two candidates, Cindy Hyde-Smith and Mike Espy, was held on November 27, 2018, in which Hyde-Smith defeated Espy. Despite her reasonable margin of victory, Hyde-Smith significantly under-performed Mississippi's partisan lean, as well as Wicker's 20-point margin of victory, held concurrently with the first round of the special election, in which the GOP candidates won a combined total of 58% to the combined Democratic total of 42%. Espy's 46.4% vote share in the runoff is, as of , the best Democratic performance in a United States Senate election in Mississippi since 1982.
