He was accused of sexual assault by at least two women during a contentious and historic Supreme Court nomination process, but the three key swing votes mean he will now have enough support when the US Senate votes on Mr Kavanaugh's confirmation over the weekend.
The federal circuit judge narrowly scraped through a procedural vote on Friday, with 51 senators supporting his nomination moving forward to a final vote and 49 opposing — the narrowest threshold for a Supreme Court nominee in modern history.
Later, Mr Flake, who previously forced the Republican majority to delay Mr Kavanaugh's vote one week to allow for an FBI investigation into the sexual assault claims made against him, said he would vote for the nominee barring any major changes.
Shortly after his announcement, Ms Collins held a highly-anticipated 3pm speech in which she emphasised why she was planning to support Mr Kavanaugh.
"I do not believe that these charges can fairly prevent Judge Kavanaugh from serving on the Court," the senator said, referring to allegations made by Christine Blasey Ford and others. She went on to describe Dr Ford’s testimony as "sincere, painful and compelling."
"Nevertheless, the four witnesses she named could not corroborate" her accusations, Ms Collins added.
The senator also laid out several examples of Mr Kavanaugh's track record as a federal circuit judge, celebrating his support for cases like Brown vs Board of Education of Topeka.
After Ms Collins announced her support for Mr Kavanaugh, a crowd pac website to fund her opponent in the 2018 midterm elections was flooded with users, causing the page to repeatedly crash. Reports indicated her future opponent had surpassed $2m during her lengthy speech.
A few minutes after Ms Collins' nearly 45-minute speech, Mr Manchin, a West Virginia Democrat, announced he would vote "yes" as well.
"I have reservations about this vote given the serious accusations against Judge Kavanaugh and the temperament he displayed in the hearing,” Mr Manchin said in a statement. “However, based on all of the information I have available to me, including the recently completed FBI report, I have found Judge Kavanaugh to be a qualified jurist who will follow the Constitution and determine cases based on the legal findings before him."
In an interview with reporters immediately after announcing his decision, Mr Manchin was met with screaming protestors who shouted, "Shame!" and "Look at me!". Near the close of the interview, one protestor yelled at the Democrat, "What is wrong with you?"
"I do hope that Judge Kavanaugh will not allow the partisan nature this process took to follow him onto the court," Mr Manchin continued.
The Supreme Court nomination process to potentially confirm Donald Trump's second pick to the court has devolved into a "circus," several senators have said.
Lisa Murkowski, a crucial swing vote who opposed the advancement of the nomination during a procedural vote on Friday morning, was lambasted as the sole Republican to vote against Mr Kavanaugh. In a tweet, Sarah Palin appeared to challenge the senator of Alaska to a primary race during her next election, writing, "Hey @LisaMurkowski, I can see 2022 from my house."
Scores of protestors have been arrested throughout the days since Dr Ford's testimony, with demonstrations continuing across Capitol Hill and celebrities like Amy Schumer and Emily Ratajowski being detained for their activism. The high-profile events appeared to take over Senate offices, with countless stand-ins at the offices of Mr Flake and other key swing senators focused on sexual assault survivors and their stories.
Meanwhile, Democratic lawmakers have decried the FBI's investigation into sexual assault claims against Mr Kavanaugh. Dianne Feinstein, the ranking member of the Senate Judiciary Committee and the first senator to receive notice of the accusations, described the probe as "incomplete" during a speech ahead of Friday's procedural vote. Dr Ford's attorneys said she had not been contacted by the federal agency during its investigation, along with numerous former roommates and college friends of Mr Kavanaugh.
Several of those longtime associates of the judge have said he was not fully truthful in his testimony, pointing to his alleged excessive drinking throughout high school and college, as well as numerous references to alcohol in his yearbook.
Mr Kavanaugh published an article in the Wall Street Journal ahead of the Friday procedural vote, titled "I am an independent, impartial judge."
"I was very emotional last Thursday, more so than I have ever been," he wrote. "I might have been too emotional at times. I know that my tone was sharp, and I said a few things I should not have said. I hope everyone can understand that I was there as a son, husband and dad. I testified with five people foremost in my mind: my mom, my dad, my wife, and most of all my daughters."
The US Senate will now schedule its vote for the weekend, expected to arrive on Saturday after lawmakers debate the nomination. The Senate Judiciary Committee has allotted 30 hours of debate before a final vote on Mr Kavanaugh.
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