Mike Pence will go head-to-head with his former boss Donald Trump after the one-time vice president filed to run for the Republican 2024 White House nomination.
The campaign will see the two former running mates vying for the chance to take on Joe Biden in the election next year.
The 63-year-old evangelical Christian, who will also have to pip Ron DeSantis, the Florida governor, filed papers with the US Federal Election Commission on Monday.
Mr Pence’s campaign launch will be on Wednesday in Des Moines, Iowa. He will take part in a CNN town hall afterwards.
He is expected to rely on a more traditionally conservative voice to separate his campaign from the populist narratives of Mr Trump and Mr DeSantis.
Policies he is likely to champion will include free trade - what Mr Pence will call “free trade with free nations” - and a national abortion ban.
‘Resist the siren song of populism’
Mr Pence will also differentiate himself from his rivals with clear backing for Ukraine against Russia, which he sees as part of a new Cold War.
He previously told the New York Times: “There’s a bit of a movement afoot in the Republican Party that would abandon our commitment to being the leader of the free world and that questions why we’re providing military support in Ukraine.”
He added: “We have to resist the siren song of populism unmoored to conservative principles.
“People want to see us get back to having a threshold of civility in the public debate.”
Mr Pence was vice president to Mr Trump between 2017 to 2021, honing his reputation as an unwaveringly loyal deputy who brought the religious Right into the tent and who was willing to defend the president against any accusation.
But he became a pariah to Mr Trump after rejecting the Republican leader’s demands that he overturn the 2020 election in his role as president of the Senate.
Berated constantly by Mr Trump after Mr Biden’s victory - and even heckled with chants of “traitor” at a conservative conference in Florida - Mr Pence had continued to praise his rival in public.
That eventually changed as Mr Trump’s torrent of false claims of election fraud led to a mob chanting for Mr Pence to be hanged at the US Capitol.
Since the riot, Mr Pence has called out Mr Trump for endangering his family and others.
Former vice president faces uphill battle
With opinion polls placing him in a distant third place, the former vice president has an uphill battle in the coming months.
The Democrats responded to Mr Pence’s bid on Twitter, saying: “Mike Pence was Trump’s MAGA wingman for four years - and he’s promised to take their extreme agenda even further.”
Mr DeSantis has consistently been polling almost 20 points above Mr Pence and is hoping to outflank Mr Trump from the Right.
Former Gov. Chris Christie and Gov. Doug Burgum of North Dakota are also set to declare their bids this week.
Mr Pence has spent much of the last two years touring early-nominating states such as Iowa, South Carolina and New Hampshire to reinforce his political vision as a “Christian, conservative, Republican - in that order”.
While his politics are popular within the party, critics question whether Mr Pence has a constituency in a party that is more focused now on populism and cultural politics than traditional conservatism.
“The Trumpists are angry with him. The Never Trumpists are mad at him for his being part of the administration and support of an impeached, convicted insurrection promoter,” Republican strategist Chip Felkel told Vox.
“It’s a hard path.”