Whitman said in a LinkedIn post on Tuesday night that, "Donald Trump's demagoguery has undermined the fabric of our national character."
"As a proud Republican, casting my vote for president has usually been a simple matter," Whitman wrote. "This year is different. To vote Republican out of party loyalty alone would be to endorse a candidacy that I believe has exploited anger, grievance, xenophobia and racial division."
Whitman, a billionaire who waged an unsuccessful gubernatorial campaign in California in 2010, said that the GOP presidential nominee's "reckless and uninformed positions on critical issues - from immigration to our economy to foreign policy - have made it abundantly clear that he lack both the policy depth and sound judgment required as president."
"Therefore, I have decided to support Hillary Rodham Clinton," she wrote, adding that it was clear that the Democratic nominee's temperament, experience and commitment to U.S. "bedrock national values" made her a better candidate.
Whitman had previously made clear she was concerned by Trump's bid for the White House, telling CNBC in May that she believed the real estate mogul's trade policies would hurt the U.S. economy, risking a possible recession.
The businesswoman's snub came after a bruising few days for Trump, in which he has struggled to dampen the furore over insulting comments he made about the family of a Muslim American army captain killed in the Iraq War. He also stumbled over questions on his relationship with Russian President Vladimir Putin, appearing to say on an ABC interview that Russia had not seized the Crimea.
Former U.S. President George W. Bush also critiqued the policies of "isolationism, nativism and protectionism" at an event on Tuesday, although he didn't mention Trump by name, The Wall Street Journal reported.
Meanwhile, his relationship with the Republican party leadership remains strained. Trump told The Washington Post that he had not endorsed Republican House Speaker Paul Ryan as Ryan contests the Republican primary in Wisconsin, while Ryan's office insisted the congressman had not sought Trump's endorsement.
The blows to Trump's campaign came as he lagged Clinton in the polls. The latest NBC News/Survey Monkey Tracking Poll showed that Clinton made gains in every census region across the U.S. over the past week, leading Trump by 8 points on August 2.