The November 22, 1963 assassination -- an epochal event in modern US history -- has spawned multiple theories challenging the official version that Kennedy was killed a lone gunman, Lee Harvey Oswald.
So the release of all the secret documents has been eagerly anticipated by historians and conspiracy theorists alike.
Trump's announcement followed reports that not all the files would be released, possibly to protect still relevant intelligence sources and methods.
But Trump appears to have decided otherwise.
"Subject to the receipt of further information, I will be allowing, as President, the long blocked and classified JFK FILES to be opened," he said in the tweet.
The files are due to be opened in their entirety Thursday nearly 54 years after Kennedy's assassination in Dallas -- unless the US president decides otherwise.
Millions of classified Kennedy files have been made public under a 1992 law passed in response to a surge in public demand for disclosure in the wake of Oliver Stone's conspiracy-heavy movie on the assassination.
But the law placed a 25-year hold on a small percentage of the files that expires October 26.
Some reports put the number withheld at 3,100. Tens of thousands of files that had been released with portions blacked out are also set to be fully declassified.
Traumatic turning point
Kennedy was only the fourth US president to be cut down by an assassin's bullets, and his death at age 46 proved a traumatic turning point as the United States headed into a period of turbulence over civil rights and the Vietnam War.
The shocking images of Jacqueline Kennedy cradling her mortally wounded husband in the back of an open presidential limousine froze the moment in the public consciousness.
A ten-month investigation led by Supreme Court chief justice Earl Warren concluded that Oswald, a former Marine who had lived in the Soviet Union, acted alone when he fired on Kennedy's motorcade, hitting the president with two shots, one through the upper back and the other in the head.
Oswald, arrested two hours later after murdering a Dallas police officer, was shot to death two days later by nightclub owner Jack Ruby as he was being transferred from the city jail.
The Warren commission's finding was challenged in 1979 by a special House investigative committee that concluded Kennedy was "probably assassinated as a result of a conspiracy" and there were likely two shooters.
Trump's conspiracy theory
A welter of conspiracy theories have arisen over the years, variously blaming Fidel Castro, the Mafia, the KGB, Lyndon Johnson and the CIA.
Oliver Stone's controversial 1971 movie "JFK" managed to implicate Johnson, the Mafia and the CIA.
Trump himself tapped into the public fascination with the case during last year's presidential campaign, bizarrely linking Republican rival Senator Ted Cruz's father to the Kennedy assassination.
"His father was with Lee Harvey Oswald prior to Oswald's being -- you know, shot," Trump said in a May 2016 telephone interview with Fox News.
"I mean, what he was doing -- what was he doing with Lee Harvey Oswald shortly before the death? Before the shooting?" Trump continued. "It's horrible."
Cruz called the accusation "nuts."
"Yes, my dad killed JFK, he is secretly Elvis, and Jimmy Hoffa is buried in his backyard," he said sarcastically, speaking to reporters at a campaign event in Indiana.
Democratic congressman Adam Schiff recalled that history Saturday, retweeting Trump's announcement and asking "does this mean Ted Cruz's father will be exposed?"