Saying Trump is "guilty of an appalling abuse of public trust," Romney became the first senator ever to vote to convict a president of his own party.
Romney split his vote on the articles of impeachment: guilty on abuse of power and not guilty on obstruction of Congress.
In a dramatic speech just two hours before the Senate took its final votes on the articles, an emotional Romney invoked his faith as a key reason guiding his decision.
"As a senator juror, I swore an oath before God to exercise impartial justice. I am profoundly religious. My faith is at the heart of who I am," Romney said in a Senate speech, before getting choked up and taking a brief pause.
"I take an oath before God as enormously consequential. I knew from the outset that being tasked with judging the president, the leader of my own party, would be the most difficult decision I have ever faced. I was not wrong."
He continued, "Accordingly, the president is guilty of an appalling abuse of public trust. What he did was not perfect. 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."
As Romney was speaking on the Senate floor, the White House abruptly cancelled an Oval Office photo op Trump was scheduled to have at the same time with Juan Guaido, the Venezuelan opposition leader the administration is touting to replace President Nicolas Maduro -- whom Trump is trying to drive out.
Reporters would have been in the room to ask Trump questions. The photo op was added to Trump's public schedule earlier Wednesday after Guaido appeared as a "surprise" guest at the president's State of the Union address, although an administration official said the visit had been in the works for two weeks.
"Given that in neither the case of the father nor the son, was any evidence presented by the president's counsel that a crime had been committed, the president's insistence that they investigated by the Ukrainians is hard to explain other than as a political pursuit. There's no question in my mind that were their names not Biden the president would never have done what he did," he said.
Addressing the president's defense, he said, "The defense argues that the Senate should leave the impeachment decision to the voters. Well, that logic is appealing to our democratic instincts, it is inconsistent with the constitution's requirement that the Senate, not the voters try the president."
"The grave question the Constitution tasked senators to answer is whether the president committed an act so extreme and egregious that it rises to the level of a high crime and misdemeanor. Yes, he did. The president asked a foreign government to investigate his political rival. The president withheld vital military funds from that government to press it to do so. The president delayed funds for an American ally at war with Russian invaders. The president's purpose was personal and political," Romney said.
"You see, I support a great deal of what the president has done. I voted with him 80% of the time, but my promise before God to apply impartial justice required that I put my personal feelings and political biases aside. Were I to ignore the evidence that has has been presented and disregard what I believe my oath and the Constitution demands of me for the sake of a partisan end, it would, I fear, expose my character to history's rebuke and the censure of my own conscience," he said.
Romney said that he expects to be denounced by his Republican colleagues for his vote to convict, but asked the chamber, "Does anyone seriously believe that I would consent to these consequences other than from an inescapable conviction that my oath before God demanded it?"
"I acknowledge that my verdict will not remove the president from office. The results of this Senate court will, in fact, be appealed to a higher court, the judgment the American people," he said.
"My vote will likely be in the minority in the Senate, but irrespective of these things, with my vote, I will tell my children and their children that I did my duty to the best of my ability believing that my country expected it of me. I will only be one name among many, no more, no less, to future generations of Americans who look at the record of this trial. They will note merely that I was among the senators who determined that what the president did was wrong, grievously wrong," he said as he concluded.
Romney explained more in an interview with Fox News' Chris Wallace taped Wednesday morning that aired following his floor speech. In the interview, as in the Senate chamber, Romney invoked his faith, although he admits "the blowback will have consequences not just for me but for my family."
"There is a hymn, do what is right and that the consequence follows. I know in my heart that I'm doing what's right," Romney said. "The worst thing that already happened me politically was losing the presidency in 2012. I have broad enough shoulders to be able to weather personal changes in my career, political or otherwise. What I don't have is the capacity to ignore my conscience."
Republicans -- as Romney predicted -- were quick to denounce him.
"Mitt Romney is forever bitter that he will never be POTUS. He was too weak to beat the Democrats then so he’s joining them now. He’s now officially a member of the resistance & should be expelled from the @GOP," Donald Trump Jr. tweeted.
But he won praise from Democrats.
"I sat silently across the chamber, listening to my friend give one of the most important speeches I have ever had the good fortune to hear in person. At a time when many wonder what honor is left in public life, there stands Mitt Romney," Sen. Chris Murphy, D-Conn., posted to Twitter.
ABC News' Trish Turner, Ben Siegel, Justin Fishel, Megan Hughes, Will Steakin, Mariam Khan and Ben Gittleson contributed to this report.