Kennedy was shot by a sniper during a visit to Dallas, Texas, in 1963
With the publication of some 13,173 files online, the White House said more than 97% of records in the collection were now publicly available.
No huge revelations are expected from the papers, but historians hope to learn more about the alleged assassin.
Kennedy was shot during a visit to Dallas, Texas, on 22 November 1963.
A 1992 law required the government to release all documents on the assassination by October 2017.
On Thursday, President Joe Biden issued an executive order authorising the latest disclosure.
But he said some files would be kept under wraps until June 2023 to protect against possible "identifiable harm".
The US National Archives said that 515 documents would remain withheld in full, and another 2,545 documents would be partly withheld.
A 1964 US inquiry, the Warren Commission, found that Kennedy was killed by Lee Harvey Oswald, a US citizen who had previously lived in the Soviet Union, and that he acted alone. He was killed in the basement of the Dallas police headquarters two days after his arrest.
JFK's death spawned decades of conspiracy theories, but on Thursday the CIA said the US spy agency had "never engaged" Oswald, and did not withhold information about him from US investigators.
Long-time JFK academics and theorists have hoped the latest release would reveal more information about Oswald's activities in Mexico City, where he met a Soviet KGB officer in October 1963.
In its latest statement, the CIA said that all information held by the agency relating to his trip to Mexico City had previously been released, adding: "There is no new information on this topic in the 2022 release."
But researchers with the Mary Ferrell Foundation, a non-profit that sued to the government to release the files, said the CIA was withholding information about Oswald's time in Mexico.
The foundation said some CIA records were never submitted to the archives and therefore were not part of the batch just released.
One newly revealed document shows the president of Mexico helped the US place a wiretap on the Soviet embassy in Mexico without the knowledge of other officials in the Mexican government.
This nugget of information was hidden by redactions in a previously released version of the file, reports the BBC's US partner CBS News.
The White House said the release of the files would provide the public with greater understanding of the investigation into the assassination.
President Biden wrote in his order that "agencies have undertaken a comprehensive effort to review the full set of almost 16,000 records that had previously been released in redacted form and determined that more than 70 percent of those records may now be released in full".
The Trump administration released thousands of pages over the course of his presidency, but withheld others on the basis of national security, despite the 1992 law forcing the release of all the information by 2017.
In October 2021, Mr Biden released around 1,500 documents, but said he was keeping the others sealed.
--- Courtesy of BBC News