Flynn quit late Monday
as controversy raged over revelations that he misled Vice President Mike Pence -- who then defended him on television -- over whether he discussed US sanctions with Moscow's ambassador to the US before the inauguration. Such a move could be a breach of the law.
On a night of stunning, fast-moving drama, extraordinary even by this White House's elevated standards, Flynn's fate took on a sense of inevitability despite Trump's instinct to retain a loyal aide. By Monday evening, White House press secretary Sean Spicer issued a statement saying Trump was "evaluating the situation." His departure was confirmed hours later.
The former general's resignation -- at the start of only the fourth week of the new administration -- is an embarrassment for Trump and a blow to a White House already embroiled in internal political dramas. It deprives Trump, who has no foreign policy experience and a barely formed national security team, of his most important White House adviser charged with keeping Americans safe from foreign threats.
His departure sent shockwaves around the world, raising questions about the administration's readiness to confront any sudden national security crisis. And since Trump frequently boasted that he would install a governing team of the highest caliber, Flynn's fall from grace is certain to raise questions about the judgment of the President himself.
The potential ramifications of the Flynn saga deepened as Monday night wore on. It emerged that the Justice Department warned the White House
last month that Flynn had not been truthful about the calls with the Russian envoy and could be susceptible to Russian blackmail.
That information, disclosed to CNN by sources familiar to the matter, exposed the White House itself to questions about what officials did with the Justice Department warning and whether Trump himself was told.
Also unknown is whether Trump was aware that Flynn spoke to the Russian ambassador to the US about American sanctions imposed on Moscow late in the Obama administration to punish the Kremlin's alleged intervention in the presidential election.
"What did the President know and when did he know it?" senior CNN political analyst David Axelrod said, using a phrase made famous by the Watergate scandal.
That unanswered question will fuel bipartisan congressional concerns about the administration's relationship with Russia and conduct in the Flynn affair.
Before Flynn's resignation, Republican Sen. Marco Rubio told CNN's Manu Raju that his contacts with the Russian embassy should form part of a Senate Intelligence Committee investigation into alleged Russian meddling in the presidential election.
Adam Schiff, the ranking Democratic member of the House Intelligence Committee, said Flynn's departure had become inevitable, but also warned that the controversy was far from over.
"Flynn's departure does not end questions over his contacts with the Russians, which have been alleged to have begun well before December 29," Schiff said in a statement. "These alleged contacts and any others the Trump campaign may have had with the Kremlin are the subject of the House Intelligence Committee's ongoing investigation."
He went on: "Moreover, the Trump Administration has yet to be forthcoming about who was aware of Flynn's conversations with the Ambassador and whether he was acting on the instructions of the President or any other officials, or with their knowledge."
Apart from the national security and even legal ramifications of Flynn's conduct, there is also a personal aspect for Trump.
The former general was picked for the role of national security adviser despite his controversial past. He was fired from the Obama administration from his post as head of the Defense Intelligence Agency over claims he was a poor manager. Conservatives, however, complained that the real reason for his clash with the previous administration was over differences on Islamic terrorism.
Flynn emerged as a loyal and outspoken supporter of Trump, warning graphically on the campaign trail about the dangers America faces from terrorism. Administration officials indicated Trump did not fire Flynn.
In the end, after the revelations about Flynn and the fact that the national security adviser had embarrassed the vice president, he had little choice but to step down. Had he remained in the administration, Pence's credibility would have been seriously eroded.
Flynn said in his letter of resignation that he had apologized to both the Pence and the Trump and that his apology had been accepted.
"Unfortunately, because of the fast pace of events, I inadvertently briefed the Vice President-elect and others with incomplete information regarding my phone calls with the Russian Ambassador," Flynn said in his letter of resignation.
Trump must now move quickly to find a new national security adviser both to steady his reeling administration and the morale of his NSC and to send a signal of foreign policy continuity to US allies and enemies.
Trump on Monday named Gen. Keith Kellogg, who is already serving as NSC Chief of Staff as the interim national security adviser. A senior administration official said Kellogg, retired Gen. David Petraeus and former Vice Admiral Bob Harward are possible replacements for Flynn.
A senior official told CNN Tuesday that Harward is considered the top contender for the job.
Petraeus presents an intriguing dilemma for Trump, since he is widely respected in Washington over his stewardship of the Iraq war surge, is a consummate political player, a former CIA director and would confer immediate gravitas and credibility on a rudimentary White House foreign policy shop.
But Petraeus fell from grace over the mishandling of classified information and remains on probation. Though he would not require Senate confirmation, his appointment would open Trump to claims of inconsistency given that he lambasted his Democratic foe Hillary Clinton over her private email server during the election campaign to make the case that she was careless with the nation's top secrets.
Flynn's departure from the administration also adds new uncertainty about the direction of its foreign policy, particularly towards Russia.
The former general was seen as an advocate of Trump's plans to seek to ease the estrangement in relations with Moscow -- a stance that has mystified both Republican and Democratic foreign policy experts in Washington.
But the President has in recent days reversed some of his most searing rhetoric -- embracing the so-called one-China policy that governs US relations with Taiwan after earlier warning that it was on the table in trade talks with Beijing.
He also offered a red carpet welcome to Japan's Prime Minster Shinzo Abe -- and apparently did not follow up on his demand for Tokyo to pay more for US security protection.
So a reversal on his position on Russia should not be ruled out if a new national security adviser takes a different approach.
Politically, meanwhile, Trump's decision to let Flynn go will fuel new speculation about how he will handle other feuds that are rocking his administration. It may be too early to rule out other departures.