The nine justices' ruling could have far-reaching implications for the extent of US executive power -- and Trump's own multiple legal issues as he seeks the White House again.
And while most constitutional law experts expect Trump to suffer a legal defeat, he may already have won a political victory.
By agreeing to take the case, the court delayed -- perhaps indefinitely -- the start of Trump's trial on charges of conspiring to overturn the results of the 2020 election won by Democrat Joe Biden.
The question of whether an ex-president is immune from prosecution is an untested one in American jurisprudence because until Trump, a former White House occupant had never been charged with a crime.
"Famously, Richard Nixon engaged in criminal law-breaking," said James Sample, a constitutional law professor at Hofstra University.
"But because he resigned, and (Nixon's successor) Gerald Ford then pardoned him, we have never had to squarely address the notion of a criminal prosecution against a former president."
Special Counsel Jack Smith filed the election conspiracy case against the 77-year-old Trump in August and had been pushing hard for a March start date for the trial.
But Trump's lawyers filed a blizzard of motions seeking to postpone the case against the Republican presidential candidate, including the claim that a former president enjoys "absolute immunity" from prosecution.
Two lower courts flatly rejected that argument but the Supreme Court, which includes three justices nominated by Trump, agreed in late February to hear the case.
In one ruling, a lower court said Trump's immunity claim is "unsupported by precedent, history or the text and structure of the Constitution."
"We cannot accept that the office of the Presidency places its former occupants above the law for all time thereafter," the judges said.
- 'Jack Smith 1, Donald Trump 0' -
Sample and other legal scholars said the Supreme Court was unlikely to hold that a president enjoys blanket immunity from prosecution.
"I find it hard to believe that even this very, very conservative, very pro-Trump Supreme Court will be inclined to find in favor of an argument that says a president is completely immune, basically, no matter what he does.
"That would be a holding that would be subject to abuse by presidents of all parties.
"I think the scoreboard will read Jack Smith 1, Donald Trump 0," Sample said, adding "the election year calendar will be of greater consequence."
Steven Schwinn, a University of Illinois Chicago law professor, agreed.
"Even if the court hands Trump a decisive, unqualified defeat, the prosecution will have to scramble to get the trial before the (November) election," he said.
Randall Eliason, a former US attorney who teaches law at George Washington University, said the unique circumstances surrounding the case would justify a quick decision by the Supreme Court, although the justices may wait until the end of their current term in June to issue a ruling.
"We've never before had a situation where a defendant would potentially have the chance to cancel his own prosecution if he wins reelection," Eliason said.
"The people have a right to have these criminal charges tried, and if Trump is reelected, there's a chance they will never be tried."
Arguing for immunity, Trump has said that without it "a president will not be able to properly function, or make decisions, in the best interest of the United States of America."
Smith rebuffed that argument in a filing with the Supreme Court.
"The President's constitutional duty to take care that the laws be faithfully executed does not entail a general right to violate them," he said.
Trump also faces 2020 election charges in Georgia and has been indicted in Florida for allegedly mishandling classified information after leaving the White House.
Opening arguments began at his trial in New York on Monday on state charges of falsifying business records by paying pre-2016 election "hush money" to a porn star.
