Thousands of files newly released from the investigation shows there was no shortage of theories at the time, and the FBI and CIA doggedly chased all of them -- while finding themselves the target of suspicion as well.
The files show all arms of the US government following up each rumor and suspicion, taking them to a right-wing militia's shooting camp, probing both Nazis and communists, and tracking down New Orleans nightclub strippers named "Candy Cane" and "Kitty DeVille."
The Union of Soviet Socialist Republics, or USSR -- the predecessor of modern-day Russia -- was the first suspect.
Documents showed shooter Lee Harvey Oswald's contact with "a member of the Soviet KGB Assassination Department" at the Soviet embassy in Mexico in September and October 1963 drew much of the attention, immediately after Kennedy was killed.
A US intelligence report issued days after the assassination shows the White House learned quickly that Moscow believed Oswald to be a "neurotic maniac" serving a right-wing conspiracy trying to poison US-Soviet relations.
That did not assuage all suspicions, however, even as Moscow continued to press that view.
An intelligence report said that in Cairo on May 24, 1964, Russian leader Nikita Khrushchev made the case to celebrated newspaper columnist Drew Pearson, who was influential across Washington and whose wife had family connections to the CIA.
Khrushchev told Pearson he could not believe the simple story that both Oswald and Jack Ruby, the nightclub owner who fatally shot him, had acted alone.
"He did not believe that the American security services were this inept," according to a CIA report of the discussion.
Pearson "got the impression that Chairman Khrushchev had some dark thoughts about the American right-wing being behind this conspiracy" and rejected all arguments to the contrary.
Cuban and Russian spies, false leads, strippers, bizarre CIA murder plots and a furious FBI director.
Newly released secret records are full of intriguing details surrounding the assassination of president John F. Kennedy. But Kennedy scholars say the thousands of documents do not appear to contain any bombshell revelations about the November 22, 1963 murder that shocked the world.
President Donald Trump ordered the release on Thursday of 2,800 classified Kennedy assassination records but held back other "sensitive" documents under pressure from the CIA and FBI.
That last-minute decision left many Kennedy historians frustrated -- and provided more fuel for the thriving conspiracy industry around the shooting of the charismatic 46-year-old president in Dallas, Texas.
"I was very disappointed," said Philip Shenon, author of "A Cruel and Shocking Act: the Secret History of the Kennedy Assassination."
"Most of the documents that were released last night are documents we'd already seen before," Shenon told AFP. "We just saw them in redacted form previously."
"The really important documents, sort of the super secret documents, most of them are not part of the release," he said.
The Warren Commission, which investigated Kennedy's murder, determined that Lee Harvey Oswald -- a former Marine Corps sharpshooter -- acted alone but that conclusion has failed to quell years of speculation that others were involved.
Hundreds of books and movies such as the 1991 Oliver Stone film "JFK" have examined scores of conspiracy theories, pointing the finger at Cold War rivals the Soviet Union or Cuba, the Mafia and even Kennedy's own vice president, Lyndon Johnson.
The CIA itself was suspect. According to a memorandum written in 1975, rumors that gunman Oswald worked for the spy agency erupted within days of the assassination. Indeed, CIA documents have shown the agency was aware of Oswald.
By November 27, 1963, the agency felt the necessity to conduct its own internal probe.
In the memorandum, counterintelligence chief Paul Hartman says he combed the CIA's records, its branch offices and outposts, station chiefs and covert operations, and came up with nothing, as he reported to the agency directors a week later.
"The results showed that Lee Harvey Oswald had never had any connection whatsoever with the agency," the memo read.
But the memorandum also showed that suspicions had not died by the mid-70s. It notes CBS television was preparing a story on the CIA-Oswald connection.
Richard Helms, deputy director and then director of the CIA from 1962 to 1973, was broadsided by constant conspiracy talk.
In a previously classified 1975 deposition to the Rockefeller Commission, which investigated the CIA's assassinations of foreign leaders, Helms said that even Lyndon Johnson, who succeeded Kennedy as president, was given to bizarre theories.
"President Johnson used to go around saying that the reason President Kennedy was assassinated was that he had assassinated (South Vietnam's) President Diem and this was just justice."
A 167-page Secret Service file showed the federal agency tasked with protecting the president followed hundreds of leads on individuals.
It checked out dozens of pro-Castro Puerto Rican nationalists, anti-Castro Cubans, African American militants, Ku Klux Klan racists, Nazis, Communists and anti-Communists.
And it went through hundreds of people who made threats against, or simply sought to contact, Kennedy while he was in the White House during 1963.
They double-checked on Elizabeth Winston, who "says she has telepathic conversations with JFK," John Donovan, who threatened from prison to kill the president for "leading the country to the brink of nuclear destruction" and Joseph Wesson, who sent a threatening letter to the president but signed his neighbor's name.
They also investigated Sylvia Sterling, who had called the Kennedys saying she had the keys to the White House but lost them, and Hildegard Oliverio, who called the White House twice in 1963 insisting she was John F. Kennedy's wife.