When Joe Biden and Donald Trump face off on stage in Atlanta, it will mark the first time a sitting president and a former president have ever debated.

The two have famously squared off before, of course, in 2020, but while the candidates on stage will be the same on Thursday, the men and political circumstances are vastly different in ways that present new challenges for both.

Above all, the consequential rematch is a rare opportunity for both to dramatically change the trajectories of their campaigns heading into a close election's final months.

"I think it's going to be an historic and epic debate," presidential historian Douglas Brinkley told ABC News. "The fact is that with Trump and Biden, it's the first time ever that we've had two people that have been president going at each other."

What Americans witnessed twice in 2020 -- the first time Biden and Trump went head-to-head for the White House -- could provide clues about what to expect now in 2024 inside the CNN studio on Thursday.

The first Biden-Trump debate in 2020 was a chaotic clash filled with personal attacks. Moderator Chris Wallace of Fox News raised his voice to scold the candidates over their constant interruptions, most of which came from Trump. At one point, Biden turned to his opponent and said, "Will you shut up, man?"

Their second meeting that year was, by contrast, more civil, as some microphone muting was introduced, and allowed time for the candidates to dive deeper into policy disputes.

A key question for Thursday, then, is which version American voters will see.

"I always like to watch how the candidates treat one another," said Alan Schroeder, a professor emeritus of journalism at Northeastern University who has written several books about presidential debates.

"In this case, there's a lot of animosity between the two of them, obviously, looking at their history of having debated before," Schroeder said. "Added on to that is Trump's claim that he didn't lose the election. And so there's just this undercurrent of hostility that I'll be looking to see how that manifests itself in the debate."

The first debate in 2020 proved unpopular with viewers, and for Trump. Polls found Biden was considered the winner of both matches, and it provided a boost to his campaign.

Four years ago, it was Trump who had to defend his administration's record and low poll numbers.

This time, the burden will be on Biden to do the same.

Incumbents historically have struggled in the first debate of their reelection campaign, according to Schroeder. The trend, he said, began with Ronald Reagan in 1984 and continued with Barack Obama in 2012 and Trump in 2020.

Biden's team, preparing at Camp David this week with 90-minute mock debates and more, wants to hold Trump accountable for remarks he's made on topics ranging from reproductive rights to the economy and democracy. His team believes the debate format -- microphone muting and the lack of a studio audience -- will force Trump to engage on the issues.

Republican allies of Trump say he, too, should focus on policy and be more disciplined. Trump's preparation includes informal policy discussions with aides and experts.

For Trump, the effort to overturn his 2020 election loss and the U.S. Capitol attack that unfolded on Jan. 6 continue to shadow his political aims. His historic conviction in New York, tied to a hush money scheme during his 2016 presidential run, looms large with his sentencing just weeks away.

Plus, his role in nominating three Supreme Court justices who voted to strike down Roe v. Wade continues to have negative electoral ramifications for the Republican Party.

For Biden, low approval ratings on two key issues this cycle -- the economy (particularly inflation) and immigration -- prove a consistent challenge.

And while both men are four years older, questions about age and fitness often plague Biden more than Trump.

Kevin Madden, a Republican strategist who worked on Mitt Romney's 2008 and 2012 presidential campaigns, said he was shocked both candidates agreed to debate given the potential harm it could do to their campaigns.

"I am surprised for a number of reasons," Madden told ABC News. "First: Trump has some momentum and debates allow his opponent to have an opportunity to shift that momentum. Second: For Biden, because he is going up against somebody who doesn't play by the rules and will always be on the attack, there is a lot of risk there."

Observers on both sides commented on what success would look like for each candidate.

Can Trump be disciplined?

"The thing that's really driving a lot of voter anxiety right now, particularly those voters who haven't yet decided, is immigration and inflation," said Madden. "So, if Trump can make this a debate that really focuses on those problems and how he's going to break away from the current status quo or reverse some of the trends on those issues, that'll be a big win."

For Biden, his vigor and presentation -- how he appears -- may be just as critical as any policy message.

"Where Biden is having some struggles with voters, age always comes up," said Jim Kessler, the executive vice president for policy at the center-left think tank Third Way. "He gets an opportunity to answer that here. And a good performance goes a long way to making voters feel reassured."

On issues, Kessler said Biden "needs to exploit his advantage on health care and choice, play to withdraw on the economy and make progress on the border. That's his challenge in the debate and over the next several months."

ABC News' Selina Wang contributed to this report.