WASHINGTON — Over the past seven days, President Trump has railed against a variety of perceived foes: Dr. Anthony Fauci, news anchors Lesley Stahl and Savannah Guthrie, and the nonpartisan Commission on Presidential Debates.

On Thursday night, he will face his actual opponent, former vice president Joe Biden, in their second and final debate.

It is the president’s last opportunity, on the biggest stage, to hammer home a focused closing message and shift a race that polls show him trailing nationwide and in key states. But if the freewheeling and falsehood-laden tenor of his campaign over the last few weeks is any indication, his central challenge will be putting Biden on the defensive without getting in his own way.

“If we wake up talking about Donald Trump the morning after the debate, it’s probably not a good debate for Donald Trump,’’ said Alex Conant, a Republican strategist who advised Marco Rubio’s 2016 presidential campaign.

The last time Trump and Biden met for a debate, on Sept. 29, the president delivered a pugilistic performance, one in which his constant interruptions pushed his polling numbers further south. It prompted the organizers of the debate to take the extraordinary step of announcing they will mute each candidate’s microphone during portions of Thursday night’s debate when the other is speaking.

Republicans — including Trump’s advisers — are openly suggesting he lower the temperature on the debate stage.

“When you talk about style and you talk about approach, I do think that President Trump is going to give Joe Biden a little bit more room to explain himself on some of these issues,’’ said Jason Miller, a top adviser to the Trump campaign, on Fox News Sunday.

For Biden, who has largely eschewed in-person events this week to prepare, the debate also comes with risk. He is likely to face questions about his stance on packing the Supreme Court, as well as a barrage of criticisms from Trump about his son Hunter, who has been the subject of unverified — and unflattering — stories pushed by Trump allies in recent days. During the first debate, Biden sometimes strayed from his efforts to stay measured by calling Trump a “clown’’ and a “racist.’’

“He’s been through it once, with Trump directly,’’ said Amanda Renteria, an aide on Hillary Clinton’s 2016 presidential campaign, who recalled how Trump ratcheted up his dramatic tactics over the course of their three debates.

“In some ways, it’s making sure that Biden just stays on track,’’ Renteria said.

Some Republicans believe muting the microphones will actually help Trump, by preventing him from mounting at least some of the sustained interruptions that were so damaging for him last time.

“It’s like if somebody is drunk outside a bar outside at 3 a.m. and looking for a fight and their buddy comes and pulls them back to save them from themselves — that’s the equivalent of what the debate commission is doing,’’ said Sarah Longwell, a GOP strategist and the founder of a group called Republican Voters Against Trump that has been running ads against the president.

Longwell runs focus groups with people who supported Trump in 2016, and she said the last debate led some of them to close the door on Trump entirely.

“To the extent that Trump can turn in a more substantive performance than he’s done, treat the debate less like one of his rallies and more like an attempt to reach voters who are skeptical of him, then this is his last chance,’’ Longwell said.

The debate comes at a difficult moment for Trump. Days after the first debate, he announced he tested positive for COVID-19. He had a case so serious, he needed supplemental oxygen twice and was hospitalized at Walter Reed National Military Medical Center, then avoided answering questions about the White House’s testing protocols as the virus spread among his staff and Republican allies.

Trump has since returned to the campaign trail, where he has begged suburban women — a demographic where he is seriously lagging — to “please like me,’’ mused openly about the prospect of losing, and continued to downplay a pandemic that is surging again across the country. He pulled out of the second scheduled debate last week after organizers made it virtual because of the White House virus outbreak, and instead participated in an NBC town hall at which he sparred with Guthrie and refused to denounce the QAnon conspiracy theory.

And this week, at a time when his allies would like him to deliver a closing campaign message highlighting the economy, which is rebounding despite the pandemic — or at least his party’s steady progress toward the confirmation of Amy Coney Barrett to the Supreme Court — he made his biggest news by calling Fauci a “disaster’’ instead.

“For the life of me, I can’t figure out the purpose of picking a fight with a member of his own administration, who has the most credibility on the most important issue facing the country,’’ said Whit Ayres, a Republican pollster.

Trump has also made a point in recent days of attacking NBC’s Kristen Welker, who will moderate Thursday night. On Wednesday, he went so far as to bring up her parents, too.

“Her parents are very biased, but that’s my life,’’ Trump told reporters as he boarded Marine One on the way to a rally in North Carolina. “In the meantime, that’s the White House behind me.’’

That makes Welker the third female news anchor the president has attacked after he called Senator Kamala Harris, the Democratic vice presidential nominee, a “monster’’ last week — a pattern that seems unlikely to help him build more support with women.

“Women start to get very uncomfortable with that kind of behavior,’’ Rentería said. She added: “He is fighting everybody.’’

Trump is 10 points behind Biden in the FiveThirtyEight website’s average of national polls. He is trailing Biden in crucial states like Pennsylvania, Michigan, and Wisconsin, and running about even in polling averages of states like Iowa and Ohio that he won handily in 2016.

Ayres said it is possible for a debate to alter the trajectory of a presidential race — it happened in 1980, helping Republican Ronald Reagan defeat incumbent Democrat Jimmy Carter — but suggested that seems unlikely in a year in which the pandemic has led to a surge in early and mail-in voting.

“The challenge this time is that we’ve had so many people who’ve already voted,’’ Ayres said. “Late-breaking events will have relatively less impact.’’

Trump’s devoted base of loyalists, however, is still planning debate watch parties, and any appearance by him could pump them up before the election.

“I don’t think we’re going to get Lincoln-Douglas out of this,’’ said Bill Bretz, the chairman of the Westmoreland County Republicans, in western Pennsylvania. “I think the most important thing that can happen in this next debate is for the president and the moderator to actually get [Biden] to state some policy positions.’’

Jess Bidgood can be reached at Jess.Bidgood@globe.com.