Declaring himself unchained from party strictures, the bombastic real estate mogul publicly berated party big-wig Paul Ryan -- the speaker of the House of Representatives -- as a "weak and ineffective leader."
"It is so nice that the shackles have been taken off me and I can now fight for America the way I want to" Trump tweeted.
Relations between the Trump campaign and party leaders have always been difficult, but they have soured considerably since Democrat Hillary Clinton began to pull away in the polls two weeks ago.
The final straw for many elected Republicans was the emergence of a video in which Trump bragged about groping women. That prompted a string of disavowals and endorsement withdrawals.
Trump further alienated allies by bringing up unproven abuse allegations against former president Bill Clinton in a Sunday debate watched by tens of millions of Americans.
Trump's angry response seems to have been prompted by Ryan suggesting fellow Republicans stop defending the party nominee and focus on limiting electoral losses in Congress.
In a conference call on Monday, Ryan told congressional Republicans "you all need to do what's best for you in your district," according to one person who listened in.
WATCH: Trump's campaign teeters as House speaker Ryan won't 'defend' him
Trump began the two hour cyber outburst by claiming "polls" had shown him to be the winner of the debate.
In fact, most scientific polls showed voters believed Hillary Clinton to be the clear winner.
"Despite winning the second debate in a landslide (every poll), it is hard to do well when Paul Ryan and others give zero support!" Trump tweeted.
He followed up by saying: "Our very weak and ineffective leader, Paul Ryan, had a bad conference call where his members went wild at his disloyalty."
Democrats "have always proven to be far more loyal to each other than the Republicans."
The gloves are off
In an ominous sign for Republicans who are worried about losing control of the House of Representatives and the Senate and the survival of the party, Trump sounded a belligerent note.
"Disloyal R's are far more difficult than Crooked Hillary. They come at you from all sides. They don't know how to win -- I will teach them!"
The latest Real Clear Politics polling average has Clinton ahead by 6.5 points across the country, and the latest polls show her ahead in a slew of must-win states for Trump.
Trump's campaign has long had a no holds barred quality -- he has accused Mexican immigrants of being rapists and Muslims of being a terror threat.
But the break with Republicans and the embrace of Bill Clinton's women accusers -- who he invited to attend Sunday's debate -- may signal the start of an even more vitriolic and personal campaign.
An unsparing Trump campaign ad released Monday showed Hillary Clinton when she had pneumonia last month, coughing at the dais and stumbling as she tried to get into her motorcade after a 9/11 anniversary ceremony.
"Hillary Clinton doesn't have the fortitude, strength or stamina to lead in our world," the narrator says.
Also Monday, Trump suggested to a mostly white audience in Philadelphia, which has a large African-American population, that the election may be "stolen" by "other communities."
'Accountable'
Clinton's campaign will be eager to tether the whole Republican Party to Trump's harsh message -- which is popular with the party base but appears to have little appeal with the wider public.
"Somewhat of a civil war is breaking out in the Republican Party," said Clinton communications director Jen Palmieri. "But I think that Donald Trump didn't become the nominee of his party on his own."
She accused elected Republicans of helping to "legitimize him," adding "I think they have a lot to answer for and the voters I imagine will hold them accountable (in) House and Senate races."
Clinton herself will revive the Clinton-Gore 1992 White House ticket on Tuesday, campaigning in Miami with her husband's vice president Al Gore.
Gore has been largely absent from politics since he lost the 2000 race in Florida to George W. Bush.
His comeback in the Sunshine State is likely to focus on the "high stakes of November's election" and climate change, which Gore has spent his post White House years working on.
Clinton will have another potent surrogate out on the campaign trail Tuesday when President Barack Obama travels to Greensboro, North Carolina.
