Incumbent Democratic Senator Claire McCaskill ran for re-election to a third term.

This resulted in Republicans holding both Senate seats in Missouri for the first time since McCaskill took office in 2007.

Hawley was also the youngest incumbent senator at that time, and continued to be until the inauguration of Jon Ossoff in 2021.

[4] Cabinet-level officials with Austin Petersen with generic Republican with Vicky Hartzler with Blaine Luetkemeyer with Todd Richardson with Eric Schmitt with Jason Smith Sen. McCaskill conceded a few hours after the polls closed on election day.

[116] Hawley won five of eight congressional districts, with the remaining three going to McCaskill, including one that elected a Republican.