What Flake said publicly is what Republican leaders are stressing over privately. They fear Trump is taking the party in a direction that could make it unelectable.
Of course, Trump would argue that he's taking the party in the right direction.
What's not up for debate is that, for better or for worse, the ground the GOP rests upon is shifting underneath Republicans' feet, and the battle is on for which side will ultimately lay claim to it.
Here are five ways that battle is manifesting right now:
1. Primaries, primaries, primaries: Senate Republicans should have a lot of pickup opportunities in next year's midterm elections, when 10 Senate Democrats are up for reelection in states that Trump won in 2016.
But Republicans first have to get through competitive primaries in nearly every state, including for seats the GOP already holds. Fighting each other for seats was not in the establishment's game plan.
Some of these competitive primaries came into being by Trump's gravitational pull. In the swing-state of Nevada, endangered Sen. Dean Heller (R) has to beat a pro-Trump challenger before he can even think about reelection. Same in Arizona, which is one reason Flake stepped down. (More on that in a minute.)
2. The decline of establishment power: Senate Republican leaders want Moore to drop out of next month's special election in Alabama to fill the seat Attorney General Jeff Sessions vacated. Now. Better to lose a Senate seat than serve alongside someone accused of sexually assaulting teenage girls.
But Moore is still in it, with the president's blessing, no less.
This is just one high-profile example of the GOP establishment leadership's slipping power. For the past several years, campaigning against the power structure in Washington has been a winning argument, said Doug Heye, a GOP consultant.
A candidates' playbook looks something like: “Attack GOP leadership, raise money,” Heye said. That has cost the GOP establishment in reputation and leverage.
3. The rise of more controversial candidates: The establishment GOP leadership once thought it had a different insurgency, the tea party movement, under control. Until interim Sen. Luther Strange lost to Moore in Alabama this fall, the Republican establishment hadn't lost a primary in five years.
They lost Alabama, and they could lose more primaries next year, which could cost them general elections. Trump's former chief strategist, Stephen K. Bannon, has said he wants to try to challenge nearly every GOP senator up for reelection in the 2018 midterms.
Though there's no evidence Bannon can do that, there is a ton of evidence that when far-right candidates win primaries, they are prone to spectacular downfalls in the general elections.
Democrats won key Senate races in Missouri and Indiana in 2012 because Republican voters elected flawed candidates who said controversial things about rape. Now, there's a growing chance Democrats could pick up a Senate seat, in Alabama of all places, because Republicans there nominated Moore.
4. Swing groups are souring on the president: Trump's approval rating at this point in his presidency is lower than any president in the history of polling. And a recent Washington Post-ABC News poll finds majorities in crucial swing groups — white women with college degrees, moderates and independents — don't like him.
If these critical voters are so turned off by Trump, Republicans up for election next year may have to decide they need to be critical of the president, too, if they want to win.
We got a glimpse of these key demographics trend away from Republicans in Virginia's state elections earlier this month. In the hotly contested governor's race, exit polls showed women voted for the Democrat by a 22-point margin, five points more than they voted for Hillary Clinton a year earlier. Independents also voted for the Democrat for governor by a larger margin than they voted for Clinton.
5. Jeff Flake himself: Some Republicans up for reelection may have to ditch Trump to keep their jobs.
The opposite happened to Flake. He quit his job to ditch Trump. “I will not be complicit,” Flake said in a shocking retirement announcement on the Senate floor last month.
But as Flake himself acknowledged, Arizona Republican voters seem to feel differently. Polls showed Flake would struggle to win a primary against his pro-Trump challenger, and Flake chose to retire rather than run for reelection in a losing effort.
“The path that I would have to travel to get the Republican nomination is a path I'm not willing to take, and that I can't in good conscience take,” he told the Arizona Republic.
The end of Flake's own career is a microcosm of the Republican Party's breakup: Republicans are in a battle for the soul of their party. And it's not clear (yet) which side will ultimately claim it.
But as Flake voiced this week, plenty of establishment Republicans are terrified that Trump could be winning.
Polling analyst Emily Guskin contributed to this report.