Flake, who has criticised the path the Republican Party has taken under Trump, said the impulse “to threaten and scapegoat” could turn America and the GOP into a “fearful, backward-looking people” and a “fearful, backward-looking party.” Flake didn’t mention Trump by name, but his remarks were unmistakably aimed at the president and his administration.

He said he “will no longer be complicit or silent”.

Flake, a former House member, is a conservative who favours limited government and free markets has been known to work on bipartisan legislation. Most notably, he joined Democrats and Republicans on legislation aimed at finding a path to citizenship for the 11 million immigrants living in the United States illegally.

“A political career does not mean much if we are complicit in undermining these values,” he said. He received applause at the conclusion of his remarks, which mirrored the themes Flake detailed in his recent book, an anti-Trump manifesto titled “Conscience of a Conservative.” The senator regretted his party’s failure to stand up to Trump in last year’s presidential race.

But Flake would have faced an uphill fight for re-election. GOP voters are in an anti-incumbent mood, heightened by the failure of Republicans in Washington to make good on seven years of promises to scrap President Barack Obama’s health care law.

The senator’s extraordinary speech came shortly after Trump had joined Senate Republicans at their weekly policy luncheon – and a few hours after the president had engaged in a war of words with another retiring Republican senator, Bob Corker of Tennessee.

As Flake spoke, Corker sat in the chamber next to Senator John McCain, Arizona’s six-term senator who’s also tangled frequently with Trump. McCain called Flake “a man of integrity, and honour and decency” and said he stood up for what he believed in “knowing full well that there would be a political price to pay.”

Republicans and Democrats said they were sorry to see Flake go.

“It is one of the most depressing things that has happened during my time in the Senate,” said Democrat Senator Michael Bennet of Colorado, who worked closely with Flake on bipartisan immigration legislation.

Moderate Republican Senator Susan Collins of Maine said she was “extraordinarily disappointed” and called Flake a “person of utmost integrity.”

White House press secretary Sarah Huckabee Sanders said of Flake’s speech: “A lot of the language, I didn’t think, was befitting of the Senate floor.”

After bucking Trump in a state the president won, Flake has been bottoming out in polls. Republicans may be left with a hard-core conservative challenger who might win the primary but lose in the general election.

Flake was facing a challenge from former state Senator Kelli Ward, who failed in her effort to take out McCain last year but has gained some traction this year. Last week, former Trump strategist Steve Bannon attended a fundraiser for her.

Ward said in a statement: “Arizona voters are the big winner in Jeff Flake’s decision to not seek re-election.” She pledged to be “a strong conservative in the US Senate who supports President Trump and the ‘America First’ agenda.”

The PAC linked to former White House adviser Steve Bannon crowed about a “monumental win” with Flake’s retirement and called it “another warning shot to the failed Republican establishment that backed Flake and others like them that their time is up.”

But mainstream Republicans in Arizona don’t believe Ward can beat Representative Krysten Sinema, who is running in her primary as the only well-known Democratic candidate. They’ve been searching for another candidate to take on Flake, and his decision to step aside opens the door wide.