The Maine politician, who voted with Democrats on whether to allow witnesses in Mr Trump's impeachment trial, announced in a floor speech that she intends to vote to acquit the president on two House-approved charges of misconduct.
Her announcement came 24 hours before the Senate is expected to vote to clear the president and about 24 hours after Mr Schiff, House Democrats' lead impeachment manager, delivered an impassioned floor speech as he closed his side's case.
"Every single vote, even a single vote by a single member, can change the course of history," Mr Schiff said, almost begging a single GOP senator to buck the brash Republican president who remains uber-popular with conservative Americans.
"It is said that a single man or woman of courage makes a majority," Mr Schiff said. "Is there one among you, who will say, 'Enough?'"
It was not enough to pull Ms Collins, who is expected to have a close re-election fight this autumn, to the Democrats' side.
"Impeachment of a president should be reserved," she said, to instances that call for such an "extreme step" of convicting and removing a sitting chief executive.
Like other Republicans who will vote to acquit Mr Trump, Ms Collins said his actions toward Ukraine were "improper" but failed to clear the "high bar" of removing him over the first article, that he abused the power of his office.
On the second article, that he unjustly stonewalled Congress, she said House Democrats failed to conduct their investigation into the Ukraine affair by opting against issuing subpoenas for the testimony of some current and former Trump administration officials. (Republicans late last week blocked the Senate from doing so to compel testimony from former White House national security adviser John Bolton and Acting Chief of Staff Mick Mulvaney.)
The Maine senator paints herself as one of the chamber's few remaining moderates, sometimes voting with Democrats on procedural matters while siding with her own party on definitive policy or nomination votes. She will do just that once again on Wednesday when the Senate will vote on two articles of impeachment against Mr Trump.
Her announcement came after Senate Majority Leader Mitch McConnell laid out his reasons for acquitting the president.
"House Democrats gave in to a temptation that every previous House has resisted. They impeached a president without even alleging a crime known to our laws," he said during his session-opening remarks. "I do not subscribe to the legal theory that impeachment requires a violation of a criminal statute. But there are powerful reasons why, for 230 years, every presidential impeachment did allege a criminal violation.
"The House Managers argued that the president could not have been acting in the national interest because he acted inconsistently with their own conception of the national interest, a conception shared by some of the president's subordinates," the Kentucky Republican said. "This does not even approach a case for the first presidential removal in American history."
Ms Collins spoke about five hours before Mr Trump is scheduled to deliver his annual State of the Union address to a joint session of Congress. But don't expect him to use the i-word.
"I read the speech, and the word 'impeachment' is not in it," Principal Deputy White House Press Secretary Hogan Gidley told Fox News.
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