When Harshbarger took office on January 3, 2021, she became the fifth woman elected to Congress from Tennessee, but only the third who was not a stand-in for her husband, after Diane Black and Marsha Blackburn.

Harshbarger focused her campaign on fixing the opioid crisis, advocating anti-abortion legislation, and protecting religious freedom.

[13] During the Republican primary, her opponents criticized her over her alleged involvement with American Inhalation Medication Specialists (AIMS), a business her husband ran that sold mislabeled pharmaceuticals from China.

[13] In 2013 Robert Harshbarger pleaded guilty to fraud charges related to the company and was sentenced to 48 months in federal prison, in addition to over $800,000 in restitution and over $400,000 in asset forfeiture.

Later that evening, Harshbarger joined 139 other Republican House members in voting to sustain objections to the certification of the results of the 2020 U.S. presidential election, based on claims of voter fraud.

In September 2021 Harshbarger co-sponsored a resolution by Marjorie Taylor Greene to impeach President Joe Biden over the withdrawal of United States troops from Afghanistan.

[41] Her husband pleaded guilty to federal charges of distributing misbranded drugs from China to kidney-dialysis patients; he was sentenced to 4 years in prison and ordered to pay restitution of $848,504 and a $25,000 criminal fine, in addition to forfeiting $425,000 in cash.

On July 30, 2024, her husband was issued a summons by the Sullivan County judicial commissioner after he was found trying to remove campaign signs from state Senator Jon Lundberg, their son's primary opponent.