The president has "a right to have a Secretary of Defense whose views are better aligned with yours," Mattis said in his resignation letter to Trump Thursday.
Defense Secretary James Mattis has resigned. Here’s the letter: pic.twitter.com/e2PulyXpXZElizabeth McLaughlin (@Elizabeth_McLau) 20 décembre 2018
His announcement came a day after Trump said he was withdrawing troops from Syria – a decision Mattis is understood to oppose.
Similarly, Trump's plans to withdraw at least 5,000 of the 14,000 US troops in Afghanistan is also thought to have been a contributing factor to Mattis' depature.
One of a number of generals appointed to key roles, including former national security adviser H.R. McMaster, and White House Chief of Staff John Kelly, Mattis' experience and stability were widely seen as a balance to an unpredictable president.
"The last adult in the playground has gone," Scott Lucas, a professor of International Politics at Birmingham University told RFI. "Trump had this admiration for military men, and the idea was that they could keep control of a president who was not very well informed."
All have now left or have one foot out the door.
Syria the last straw
For Mattis, the last straw came when Trump ordered the complete withdrawal of America’s 2,000 troops from Syria, declaring that the Islamic State armed group had been “defeated”.
We have defeated ISIS in Syria, my only reason for being there during the Trump Presidency.Donald J. Trump (@realDonaldTrump) 19 décembre 2018
"Trump did this so unpredictably and whimsically against all the advice from his military and civilian advisors, with no regard for the consequences of what that move would be," comments Lucas.
Immediately after Trump's claim that the IS militant group in Syria had been vanquished, his allies France, the UK and Germany responded that the Islamic State remains a threat and could re-emerge.
Republicans have warned the US pullout would jeopardise the fight against IS and undermine America's hopes of countering Iran and Russia's influence in Syria.
It may also embolden Turkey to launch a major offensive against America's Kurdish allies in the north of the country, says Lucas. "Now that the US is walking away, that frees up Turkey to intervene, which could lead to more refugees, more displaced, more destruction."
France to stick it out in Syria
US officials have long fretted about leaving Syria before a peace agreement can be reached to end the country's brutal eight-year civil war.
Meanwhile, French defence forces have vowed to maintain their operations in Syria where some 75 special forces are currently deployed, as reported by the daily Le Monde.
Defence Minister Florence Parly wrote in a tweet Thursday: "Islamic State has not been wiped from the map, nor does it have its roots elsewhere. The last pockets of this terrorist organisation must be defeated militarily once and for all."
However, analysts warn that without the US, the military burden on its allies may be too heavy to shoulder.
"France and the UK are now effectively stranded because while they do have some special forces inside Syria, it's a far smaller presence than the 2,000 American personnel," says Lucas.
Allies lose trust
"Most importantly, the UK and France just don't have the air capabilities that the Americans have in terms of anti-terror operations and also as a deterrent to Turkey and the Assad regime."
In his letter, Mattis criticised Trump for failing to value America’s closest allies, who fought alongside the United States in both conflicts.
Without maintaining those alliances, he wrote, "we cannot protect our interests or serve" the role of an "indispensable nation in the free world."
The Trump administration has tended to lash out at America's allies in France, while at times appearing to side with US adversaries, like Russia over his own officials.
Trust at stake
"The wider consequence for France here is that, it's not just a question of losing the US as a reliable partner," comments Lucas.
"If you can't count on the Americans in the Middle East, because Trump is more prone to embrace Vladimir Putin rather than stand up to him, can you really count on the American military if things get hot in Eastern Europe?" he asks.