The GOP challenger, Kelly Tshibaka, has led the Alaska Department of Administration since early 2019.
An early Republican candidate announced plans Monday to seek the Alaska U.S. Senate seat that has been held since 2002 by Republican Sen. Lisa Murkowski.
Kelly Tshibaka, who has led the sprawling Alaska Department of Administration since early 2019, in a statement said she is running "for the Alaskans who believe government is of the people, by the people and for the people. The D.C. insiders need to be held accountable to us."
Her campaign said she was resigning as commissioner in pursuing the Senate race.
Murkowski is widely seen as a moderate and has at times been at odds with her party, including on issues like abortion and in her criticism of Donald Trump.
Murkowski was one of seven Republican senators who voted to convict Trump, who was acquitted in a trial last month of a charge of incitement of insurrection related to the Jan. 6 U.S. Capitol riot.
Earlier this month, state Republican Party leaders voted to censure Murkowski over that vote, with party leaders in some other states taking similar actions against Republicans who voted as she did.
Murkowski, speaking to reporters in Juneau last month, did not directly answer whether she would seek reelection next year.
She said she is "doing what I should be doing to ensure that I have that option and that opportunity to run for yet another term." She said she is "absolutely leaving the avenues open for my reelection opportunities."
Tshibaka is among those who have been seen as possible candidates for the U.S. Senate race and over the last year or so has sought to raise her profile. She has used social media to promote her department's work, highlight her family and faith, express support for Republican candidates, and outline stances on issues such as gun rights.
Tshibaka has overseen a vast department, with agencies including the Division of Motor Vehicles, Personnel and Labor Relations, and the office that maintains technology infrastructure for the state executive branch. Tshibaka has at times butted heads with unions and with lawmakers over procurement issues or a proposal to close some Division of Motor Vehicle offices.
Her resume includes work in the offices of inspector general for the U.S. Postal Service, Federal Trade Commission, and Department of Justice before joining Alaska Gov. Mike Dunleavy's administration.
The landscape for the 2022 elections will be different. A voter initiative passed in November scrapped party primaries for a system in which the top four vote-getters advance to the general election. It also instituted a ranked-choice voting system for general elections.
Murkowski was appointed to the Senate in 2002 by her father, Frank Murkowski, who had resigned the same seat, which he'd held since 1981, to become governor. She won a tight race in 2004 against Democrat Tony Knowles and in 2010, she lost her Republican primary to tea party candidate Joe Miller before winning the general election with a write-in campaign.
Murkowski easily won reelection in 2016 in a crowded field in which she garnered 44% of the vote.
Lindsay Kavanaugh, executive director of the state Democratic Party, said in a fundraising appeal earlier this month the party was "prepping" its efforts to "retire Lisa."
The state Division of Elections does not yet show a candidate list for next year's races.