(CNN) Lots of Cabinet officials -- and I mean LOTS -- have either resigned or been fired by President Donald Trump in his first 20 months in office. But no one has quit in quite the same way as Defense Secretary James Mattis did Thursday night .

"Because you have the right to have a Secretary of Defense whose views are better aligned with yours on these and other subjects, I believe it is right for me to step down from my position," Mattis wrote to Trump in a pointed two-page letter that he hand-delivered to the commander in chief earlier Thursday afternoon.

And then, this:

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"One core belief I have always held is that our strength as a nation is inextricably linked to the strength of our unique and comprehensive system of alliances and partnerships. While the US remains the indispensable nation in the free world, we cannot protect our interests or serve that role effectively without maintaining strong alliances and showing respect to those allies."

In that single paragraph, which sums up the sentiment of the longer letter, Mattis rejects out of hand Trump's "America First" foreign policy that had led to clashes with a slew of longtime allies -- from Germany to Britain to Australia and back. From Trump's decision to pull out of the Paris climate accord to his recent announcement that the United States would be leaving Syria -- a decision with which Mattis disagreed -- Trump has shown time and time again that he rejects the post-World War II alliance structure that presidents, Republican and Democratic, have relied upon for more than seven decades.

It's impossible to read Mattis' letter as evidence of anything but a man who had been pushed well past his breaking point and, finally, snapped. Faced with a President who made enemies of our allies and allies of our enemies -- no one has arguably been happier with the Trump presidency than Russian President Vladimir Putin -- Mattis decided to walk away.

Which is remarkable, both by itself and when you consider the broader context of how and where Mattis fit into the Trump Cabinet and administration.

In a vacuum, Mattis was widely regarded by those familiar with his approach to the office as someone who simply would not walk away without a very good reason. A much-decorated military general, Mattis was part of a group within the Trump administration -- that once included chief of staff John Kelly and Secretary of State Rex Tillerson -- who viewed their roles in the administration as a duty to the country.

Step back and you see Mattis' departure as a sort of bookend to Tillerson's removal as secretary of state, with Kelly's removal sandwiched in between. Together, those three men were cast -- by Trump and his allies -- as the crown jewels of the administration, men who had long experience in Washington and around the world and who, together, would form a shield of sorts against Trump's worst instincts in diplomacy and foreign policy.

Trump tired of Tillerson first. Once enthralled by Tillerson's time spent as a titan of industry (he was the CEO of ExxonMobil), Trump came to view Tillerson as someone who didn't understand that his job was to execute the vision of the chief executive -- period.

And Tillerson, too, was stunned at Trump's seeming lack of knowledge about not only basic geopolitics but the rule of law. "So often, the President would say here's what I want to do and here's how I want to do it, and I would have to say to him, 'Mr. President I understand what you want to do but you can't do it that way. It violates the law'," Tillerson recounted earlier this mont h.

Then came Kelly's time in the Trump vise. Heralded for his solid work at the Department of Homeland Security, Kelly was brought on as chief of staff last summe r to restore order to a West Wing that was careening out of control due to an unmanaged President. Trump, who once praised Kelly's military background and bearing, soon began to chafe under Kelly's strict policies on who could communicate with the President and what news outlets the President was allowed to consume.

Despite all of that -- losing his two most reliable and relied-upon confidants in the Cabinet -- Mattis seemed to skate above it all. He was rarely part of any drama involving Trump. He simply did his duty to the best of his ability. And for a while, it seemed as though Mattis would be the lone survivor of the Big Three from the early days of the administration.

That ended Thursday -- with the letter that seemed to be months of pent-up frustrations by Mattis loosed, in written form, on Trump.

With Tillerson gone and Mattis and Kelly on their way out, the prevailing sentiment among establishment Republicans in Washington was one of thinly veiled panic.

"We are headed towards a series of grave policy errors which will endanger our nation, damage our alliances & empower our adversaries," tweeted Florida Sen. Marco Rubio (R) shortly after the news of Mattis' resignation broke.

Nebraska Sen. Ben Sasse (R) called it a "sad day," adding: "Secretary Mattis was giving advice the President needs to hear. Mattis rightly believes that Russia and China are clear adversaries and that we are at war with jihadists across the globe who plot to kill Americans at home."

The simple fact of Trump's presidency is now this: All rails have been removed from the proverbial road. The men (and women) expected to mediate and mitigate some of Trump's wilder ideas and statements are now, almost to a person, gone -- driven off by a President whose vision of the country and the world is both highly erratic and deeply held. And almost to a person, those advisers have been replaced by others who have risen up in Trump's reckoning by telling him what he wants to hear.

Mattis' departure is the death knell of the idea that Trump could --and possibly would -- adhere to any sort of "normal" order during his term as President. This is a President who has driven away the very people who he (and the country) trusted with guiding him as a political leader in these difficult. Now there is only Trump -- and those willing to enable him.