The surprise announcement to hand the probe over to Mueller, a lawman with deep bipartisan respect, was a striking shift for Trump's Justice Department, which had resisted increasingly loud calls from Democrats for an outside prosecutor. It immediately escalated the legal stakes - and the potential political damage - for a president who has tried to dismiss the matter as partisan witch hunt and a "hoax".
Just a week ago, according to the Trump administration, Deputy Attorney General Rod Rosenstein was the most admired and unimpeachable man in America.
Sen. Chris Coons, D- Del., told The Washington Post that Rosenstein's recommendation to Trump to fire Comey puts his "credibility is on a very shaky foundation with many of my colleagues. Mr. Rosenstein has done the right thing", Senate Minority Leader Chuck Schumer of NY said on the Senate floor. He also indicated that the Russian Federation investigation had factored into his decision.
"With all of the illegal acts that took place in the Clinton campaign & Obama Administration, there was never a special councel appointed!". He did not provide examples or evidence of any "illegal acts". Trump later deleted and retweeted that statement to correct the spelling of "counsel". And President Richard Nixon resigned after a damning investigation by a select committee, before he could be impeached.
The President's tweets appear to signal a policy of resistance to Mueller's investigation, that will now likely cast a shadow over the beleaguered White House for months if not years to come.
Mueller served as Federal Bureau of Investigation director under Democratic and Republican administrations from 2001 to 2013, and is highly respected in Washington.
He denied media reports from last week that Comey had asked him for additional resources for his investigation before Trump fired him.
In Rosenstein's meetings with lawmakers, he reiterated the scathing critique laid out in his memo concerning Comey's handling of the investigation into Hillary Clinton's use of a private email server, including Comey's July news conference announcing that the FBI would not recommend charges.
"I accept this responsibility and will discharge it to the best of my ability", Mueller said in a statement.
The focus now turns to how Mueller will pick up the FBI's investigation of the Trump campaign and Russian Federation, and what it means for the White House.
Trump said Thursday that he respects "the entire thing" but said that he personally has no ties to Russian Federation.
Reactions from Congress to Mueller's appointment were mainly positive, even though Republicans had dismissed an independent outside investigation as unnecessary and duplicative of what congressional committees already are doing.
The Russia matter has consumed Washington and overshadowed Republican legislative priorities including a planned healthcare overhaul and sweeping tax cuts, something the party had hoped to make rapid progress on given its control of the White House and both chambers of Congress. The White House press briefings have in recent weeks revolved around this topic for most of the time and Mr. Trump has said he might stop the briefings altogether.