Mr Romney announced his intentions during a speech on the Senate floor, where he said he would vote to convict the president for the abuse of power charge he faces, but acquit him on the obstruction of Congress charge. In doing so, he will be the first senator in US history to vote for the removal of a president of his own party in an impeachment trial.
It appears unlikely that the announcement would significantly alter the likelihood that Mr Trump will ultimately be acquitted on both charges. But, it does denies the president and his allies the ability to cast the effort against him as a solely partisan exercise.
"The president is guilty of an appalling abuse of public trust," Mr Romney said during the speech, in which he invoked his sense of duty to argue that the Senate vote will be in-turn judged by the American people and history books. At times, he appeared to hold back tears when mentioning his being "profoundly religious" and that he had sworn an "oath before God".
"What he did was not perfect," he continued, referencing the president's claims that his actions were flawless. "No, it was a flagrant assault on our electoral rights, our national security, and our fundamental values. Corrupting an election to keep oneself in office is perhaps the most abusive and destructive violation of one's oath of office that I can imagine."
The Senate will vote on Wednesday afternoon on the articles of impeachment that were delivered from the House following their vote to make Mr Trump the third president in US history to be impeached.
Shortly after Mr Romney's announcement, the White House abruptly cancelled a planned open press meeting in the Oval Office between the president and Venezuelan opposition leader Juan Guaido. The development was billed as a change of plans, and reporters have said it appeared organised.
But, that abrupt cancellation was still met with speculation that the two decisions may be connected, and that the president was not interested in speaking to the press shortly after the surprise announcement. Officially, the White House did not immediately comment on Mr Romney's announcement, and Mr Trump's Twitter account remained silent.
Mr Romney was among a handful of senators who had been watched to see how they would vote, and is the only Republican so far to indicate he would vote to convict.
That group of watched senators includes Democrats as well as Republicans, virtually all of whom represent a state considered to be competitive. Alabama senator Doug Jones, who faces a long-shot re-election bid, said earlier on Wednesday that he would also vote to convict the president.
Susan Collins, a key swing state senator from Maine, has meanwhile announced she will vote to acquit the president.
But Mr Romney's decision also highlights the dangers of breaking from one's party during this impeachment trial, with immediate rebuke to him online with political observers calling for his dismissal from the Republican Party. Months before Mr Romney, congressman Justin Amash similarly found himself under fire for rebuking the president, and ultimately announced he would leave the Republican Party last year.
"Mitt should be expelled from the @SenateGOP conference," wrote Donald Trump Jr, the president's adult son, on Twitter after the floor speech.
Regardless, Mr Trump will almost surely be acquitted, with a removal order only becoming possible when a super majority of senators vote in favour. That would mean Democrats would need to convince around 20 Republicans to break rank and vote with them to impeach.
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