Already, after a year of clashes over political style and substance -- particularly on immigration and trade -- Trump was eager to see Flake ousted in the GOP primary in next year's midterm election. But since the publication of an excerpt of Flake's book Monday, in which Flake accuses the President of campaigning on a "late-night infomercial" that is "free of significant thought," calls for two pro-Trump politicians weighing a challenge to Flake have reached a fever pitch.
"It's getting to the point where somebody's got to make a very clear decision, instead of just talking about it," said Robert Graham, the former Arizona GOP chairman and a Trump supporter in 2016.
Flake and Trump have long been at odds. Their dramatic differences in policy and style were laid plain in Flake's new book "Conscience of a Conservative." The Arizona senator unloads on Trump in the book and concedes his own role in enabling Trump's rise to power.
"In the tweeting life of our president, strategy is difficult to detect. Influencing the news cycles seems to be the principal goal; achieving short-term tactical advantage, you bet. But ultimately, it's all noise and no signal," Flake writes.
He even touches on Trump's own prediction that their differences would cost Flake his seat. "You've been very critical of me," Trump told Flake in a summer 2016 meeting that Flake recounted in the book. At that meeting, Flake wrote, Trump predicted Flake would lose reelection.
Now, Graham and state treasurer Jeff DeWit, who was the Trump campaign's Arizona chairman in turned national chief operating officer and remains in touch with the President, are both considering entering the race and making the argument that Flake has failed to sufficiently support Trump.
Kelli Ward, the conservative who challenged Sen. John McCain in the GOP primary in 2016, has already launched her campaign against Flake.
A fight with Trump years in the making
Increasingly, Trump-aligned donors and influential Republicans in Arizona say they are eager to back a serious challenger. Calls and text messages recruiting DeWit and Graham have peaked since the excerpt of Flake's book was published Monday in Politico.
As Graham chatted with a reporter over a Cobb salad at Mimi's Cafe north of Phoenix, a name flashed for an incoming call on his iPhone screen: Michael Bidwill, a major donor whose family owns the NFL's Arizona Cardinals.
He pointed out that Trump won the 2016 Arizona Republican presidential primary with 46% support, which was more than the 38% combined earned by his two nearest competitors -- Texas Sen. Ted Cruz and Ohio Gov. John Kasich.
"I'm drinking the (Trump) Kool-Aid," Graham said. "And so when I see any obstacles to his campaign promises, that's what motivates me to move the obstacles -- remove them, right?"
In his book, Flake concedes that refusing to answer questions about Trump's tweets was "a monumental dodge." He also knocked "the strange specter of an American president's seeming affection for strongmen and authoritarians."
"If ultimately our principles were so malleable as to no longer be principles, then what was the point of political victories in the first place?" Flake asks in the book.
Flake and Trump have broken most significantly on trade and immigration policy. Flake is among the Senate's Republican advocates for comprehensive immigration reform, and a staunch defender of the North American Free Trade Agreement, which Trump has threatened to withdraw from unless Canada and Mexico agree to substantial changes.
Even the title of Flake's book -- "Conscience of a Conservative" -- mirrors the 1960 book by another Arizona senator, Barry Goldwater, that railed against the GOP and served as an ideological underpinning of the conservative movement.
"There are two parts of conservatism, fiscal policy and limited government," Flake told CNN's Jake Tapper on Tuesday. "Barry Goldwater in 1960 felt the party was straying from those principles. I think we are facing a similar crisis now, as Republicans have taken up an unfamiliar banner. This populism, in some cases xenophobia, anti-immigration, protectionism -- that's not familiar to us, and I don't think it's a governing philosophy."
A senator who's an open book
Those close to him say the book mirrors the introspective Flake they know.
Before entering the House in 2001, Flake wrote op-eds for conservative think tanks. He journals regularly. And while in the House, he regularly emailed his detailed thoughts on travel and policy to a small, private list of family and friends.
Flake didn't tell his political advisers about his book's existence until weeks before it was published. Several people who know Flake -- including supporters who are concerned that the book could damage his re-election prospects -- said they saw in the book his Mormon roots.
"He's a catalyst for the Party to have a conversation about what it means to be a conservative -- which is something we haven't done," said Chad Heywood, a former Flake staffer and Arizona GOP executive director.
From a strategic perspective, the book appears likely to help Flake more in a general election -- where Democrats see him as one of the two ripest Republican Senate targets on the ballot in 2018 -- than in a primary. The state's primary is open to independents, who make up about 15% of the electorate -- a number that Flake would like to increase.
The book is the latest chapter in a long-simmering feud between Trump and Flake, once an anti-earmarks face of the GOP's last revolution who has now become a target of the party's latest hostile takeover.
In the lead-up to the 2016 election, Flake had criticized Trump -- and Trump responded by openly musing in front of Arizona supporters about spending $10 million to unseat Flake in his August 2018 Senate primary.
Since then, Trump and his White House associates have stayed in close contact with Graham and DeWit.
Those calls haven't slowed: Both DeWit and Graham have heard from the White House within the last week.
The two men are friends who speak almost daily and have agreed not to run against each other.
DeWit could also be headed for a position in Trump's administration. He has not commented publicly on the prospect of challenging Flake because a potential Trump appointment could require Senate confirmation -- which would make angering a majority member from his home state a costly mistake.
One major question hovering over the race -- and spooking pro-Flake Republicans -- is whether Trump is willing to weigh in against Flake on Twitter or leverage his campaign's email list to raise money for a Flake challenger.
Arizona's emergence as a central battleground in the war over the Republican party's future extends beyond Flake. Last week it was his Arizona colleague, McCain, who sank Trump's biggest legislative goal by voting against the "skinny repeal" of Obamacare.
McConnell gets hit too, but he's not hitting back
Flake's book also includes clear shots at Senate Majority Leader Mitch McConnell.
"It was we conservatives who, upon Obama's election, stated that our No. 1 priority was not advancing a conservative policy agenda but making Obama a one-term president -- the corollary to this binary thinking being that his failure would be our success and the fortunes of the citizenry would presumably be sorted out in the meantime," Flake wrote, in a reference to a McConnell-designed strategy.
McConnell sidestepped a question about Flake from reporters Tuesday. "I haven't had a chance to read Senator Flake's book. I will get around to it at some point," he said.
But McConnell, R-Kentucky, is sticking with Flake -- abiding by his policy of supporting all incumbent Republican senators against primary challengers.
"Senator Flake has my total support," McConnell said in a statement.
Katie Martin, the National Republican Senatorial Committee's communications director, said the NRSC "supports Sen. Flake, as we do all our incumbent members."
"Senator Flake has been there for the President, too," said Kathy Petsas, a 2016 Republican National Committee delegate whose family has deep roots in Arizona Republican politics. She pointed to Flake's support for Neil Gorsuch's nomination to the Supreme Court and his votes for Trump's Cabinet nominees.
"If I was the President, I'd say -- he may be an S.O.B. but he's mine," she said. "And quite frankly, DeWit and Graham can't win. Flake can win the general."
CORRECTION: This story has been updated