"While my time serving in the Administration comes to a conclusion, it doesn't mean I will stop fighting for American workers," Chavez-DeRemer said in a statement posted on X, Xinhua reported.
Her departure makes her the third to depart during President Donald Trump's second term.
"Labor Secretary Lori Chavez-DeRemer will be leaving the Administration to take a position in the private sector," White House Director of Communications Steven Cheung wrote in an earlier post on X.
Deputy Secretary of Labor Keith Sonderling will take on the role of acting secretary of labor, Cheung said.
The Labor Department's inspector general's office is nearing the end of a months-long investigation into a whistle-blower's allegations of professional misconduct by Chavez-DeRemer and her closest aides, including claims that she was having an affair with a member of her security team and that she used department resources for personal trips, The New York Times reported Monday.
Chavez-DeRemer's departure follows a series of high-level shakeups under Trump.
Homeland Security Secretary Kristi Noem was fired in March, shortly after testifying before lawmakers on Capitol Hill over her agency's handling of immigration enforcement and a 220 million-US-dollar advertising campaign featuring herself.
Attorney General Pam Bondi was dismissed in April amid growing frustration over her leadership at the Justice Department and her handling of the Jeffrey Epstein files.