Mr Pence will formally launch his campaign on Wednesday in the city of Des Moines, Iowa. His candidacy was made official after filing paperwork with the Federal Election Commission.
The former vice president has spent months preparing for a White House campaign by releasing a book, speaking at various engagements and touring states across the US.
“There might be somebody else I'd prefer more,” Mr Pence said last year when asked if he would endorse Mr Trump for another run at the Oval Office.
He was a firm supporter of Mr Trump while serving as vice president but refused to do his boss's bidding when he did not concede to demands that the results of the 2020 presidential election be overturned.
Many supporters of the former president stormed the Capitol building on January 6, 2021 in the effort to block the peaceful transition of power. Some, apparently spurred on by Mr Trump, called for Mr Pence to be hanged.
Mr Pence has since said he and Mr Trump will never agree on the insurrection.
Mr Pence joins a growing list of candidates including Florida Governor Ron DeSantis, former UN ambassador Nikki Haley, US senator Tim Scott.
Former New Jersey governor Chris Christie and North Dakota Governor are also planning to seek the Republican nomination, which would bring the field to 10.
Mr Trump currently leads his rivals with about 54 per cent of Republican support, FiveThirtyEight's national polling aggregator shows.