[4] Guest ran for the United States House of Representatives in Mississippi's 3rd congressional district to succeed Gregg Harper, who chose not to seek reelection.

[9] In December 2020, Guest was one of 126 Republican members of the House of Representatives to sign an amicus brief in support of Texas v. Pennsylvania, a lawsuit filed at the United States Supreme Court contesting the results of the 2020 presidential election, in which Joe Biden defeated[10] Trump.

The Supreme Court declined to hear the case on the basis that Texas lacked standing under Article III of the Constitution to challenge the results of an election held by another state.

[11][12][13] On May 19, 2021, Guest was one of 35 Republicans who joined all Democrats in voting to approve legislation to establish the January 6, 2021 commission meant to investigate the storming of the U.S.

[15] In June 2022, after a leaked decision by the Supreme Court of the United States to revoke the right to abortion in the case of Dobbs v. Jackson Women's Health Organization, Guest wrote to the Department of Homeland Security to demand action in the wake of attacks by Jane's Revenge, which Guest called an "anarchist extremist group" that targets crisis pregnancy centers and other anti-abortion organizations.