Bradshaw, who's been close to the former Florida governor for decades and was senior adviser to his 2016 campaign, officially switched her registration to unaffiliated. She told CNN's Jamie Gangel in an email interview that the GOP is "at a crossroads and have nominated a total narcissist -- a misogynist -- a bigot."
"This is a time when country has to take priority over political parties. Donald Trump cannot be elected president," Bradshaw said.
The departure from the Republican Party of a Bush loyalist -- Bradshaw began her career working for George H.W. Bush's 1988 campaign -- is the latest sign of an influential and respected member of the GOP establishment turning against Trump.
"This election cycle is a test," Bradshaw said. "As much as I don't want another four years of (President Barack) Obama's policies, I can't look my children in the eye and tell them I voted for Donald Trump. I can't tell them to love their neighbor and treat others the way they wanted to be treated, and then vote for Donald Trump. I won't do it."
Her decision comes amid controversy over Trump's criticism of the family of an Muslim-American soldier killed
in action in Iraq in 2004. Bradshaw called that remark "despicable," saying it "made me sick to my stomach."
"Donald Trump belittled a woman who gave birth to a son who died fighting for the United States. If anything, that reinforced my decision to become an independent voter," she said. "Every family who loses a loved one in service to our country or who has a family member who serves in the military should be honored, regardless of their political views. Vets and their family have more than earned the right to those views. Someone with the temperament to be president would understand and respect that."
Bradshaw said the latest incident reinforced how she was feeling about the decision she's long weighed.
Her move goes beyond what other Republicans have said or done, although many top leaders in the GOP -- including Sen. John McCain, House Speaker Paul Ryan and Sen. Mitch McConnell, among others -- have made it clear that they have a big problem with Trump's comments about a Gold Star family. But none have, as of yet, withdrawn their endorsements or support.
"I've been considering the switch for months. Ultimately, I could not abide the hateful rhetoric of Donald Trump and his complete lack of principles and conservative philosophy," she said. "I didn't make this decision lightly -- I have worked hard to make our party a place where all would feel welcome. But Trump has taken the GOP in another direction, and too many Republicans are standing by and looking the other way."
Bradshaw served as Jeb Bush's campaign manager when Bush ran unsuccessfully for Florida governor in the early 1990s and again four years later when he won.
Bradshaw said she hasn't yet decided who she'll vote for -- though "it obviously won't be Trump. I haven't made a decision yet between Clinton, Gary Johnson or writing in a candidate."
"If the race in Florida is close, I will vote for Hillary Clinton," she said. "That is a very difficult statement for me to make. I disagree with her on several important issues. I have worked to elect Republicans to national and statewide offices for the last 30 years. I have never voted for a Democrat for president, and I consider myself a conservative, a supporter of limited government, gun rights, free enterprise, equality of opportunity. I am pro-life. There are no other candidates who were serious contenders for the nomination that I would not have supported.
"But," she said, "we are at a crossroads and have nominated a total narcissist -- a misogynist -- a bigot. This is a time when country has to take priority over political parties. Donald Trump cannot be elected president."
Analyzing the GOP primary in which Jeb Bush failed to attract a significant share of the vote and dropped out early, Bradshaw pointed to a fractured field, with Trump able to consistently capture one-third of the vote early.
"I really fault the candidates who did not speak out against Trump until the end of the primary cycle. Lindsay Graham and Jeb Bush spoke out early and consistently -- but most did not, fearful of offending that segment of the party or positioning themselves for future office," she said in her email.
Bradshaw said she sees voting against Trump as "the only real choice for reasonable, thoughtful Republicans to make."
"Our president must represent what is good about America -- a belief in opportunity for all -- regardless of race and gender and background -- to rise up and live the American dream," she said. "A president can't tear down Hispanics, or mock someone who is disabled, or use symbols in campaign literature that Jewish voters understandably find offensive. To continue to be the hope of the world, all Americans regardless of party affiliation have to reject him."
She added: "If and when the party regains its sanity, I'll be ready to return. But until Republicans send a message to party leadership that this cannot stand, nothing will ever change."