Cheney, 46, is the elder of Dick Cheney's two daughters. Her announcement is a political challenge unlike anything Wyoming has seen for years, maybe decades Republicans in the state rarely challenge incumbents in national office. All three members of the state's congressional delegation and all statewide elected officials are Republican.
Yet Cheney's interest in the seat has been an open secret for months. Last year, Cheney and her husband bought a home in the posh northwest Wyoming community of Jackson Hole. She has been in the public eye in recent years as a Fox News political commentator.
She's also been speaking frequently at Republican Party events in the state.
US Sen. Mike Enzi also announced Tuesday he was planning to seek a fourth term, making clear he was seeking re-election bid more than six months earlier than he has in the past.
"Anybody can get in the race that wants to get in the race. There's at least one person that's trying to get me to retire," Enzi said earlier this month at a constituent meeting in Pine Bluffs. He declined to say who he was referring to, "No, people can judge who they think that is themselves," he said.
Enzi, a former state legislator and mayor of Gillette, was first elected to the Senate in 1996. He said in Tuesday's announcement that he intends to concentrate on serving in the Senate until the campaign gets underway.
Cheney holds a law degree from the University of Chicago and has worked for the State Department and the Agency for International Development.