
The assassination took place at 12:30 p.m. Central Standard Time on Friday, November 22, 1963. Kennedy was fatally shot while traveling with his wife Jacqueline, Texas Governor John Connally, and Mrs. Nellie Connally in a Presidential motorcade.
At 12:29 p.m. CST, as Kennedy's uncovered limousine entered Dealey Plaza, Nellie Connally, then the First Lady of Texas, turned around to Kennedy, who was sitting behind her, and commented, "Mr. President, you can't say Dallas doesn't love you," which President Kennedy acknowledged. From Houston Street, the presidential limousine made a left turn onto Elm Street allowing it to pass to the Stemmons Freeway exit. Tt turned on Elm, passing the Texas School Book Depository. As it continued down Elm Street, shots were fired at Kennedy. The majority of witnesses recalled hearing three shots. Many later said that they first thought the first shot to be a firecracker or the exhaust backfire of a vehicle just after the president started waving.
Within one second of each other, President Kennedy, Governor Connally, and Mrs. Kennedy, all turned abruptly from looking to their left to looking to their right. Connally, a World War II military veteran like the president testified that he immediately recognized the sound of a high-powered rifle, then he turned his head and torso rightward attempting to see President Kennedy behind him. Connally testified he could not see the president, so he then started to turn forward again (turning from his right, to his left). Connally said that when his head was facing about twenty-degrees left of center he was hit in his upper right back by a bullet, fired in a gunshot that Connally testified he did not hear the muzzle blast from. After Connally was hit he then shouted, "Oh, no, no, no. My God. They're going to kill us all!"
Mrs. Connally testified that right after hearing a first loud, frightening noise that came from somewhere behind her and to her right, she immediately turned towards President Kennedy and saw him with his arms and elbows already raised high with his hands in front of his face and throat. She then heard another gunshot and John Connally started yelling. Mrs. Connally then turned away from President Kennedy towards her husband, then another gunshot sounded and she and the limousine's rear interior were now covered with fragments of skull, blood, and brain matter.
The limousine was passing a grassy knoll on the north side of Elm Street at the moment of the fatal head shot. As the motorcade left the plaza, police officers and spectators ran up the knoll and from a railroad bridge over Elm Street to the area behind a five-foot high stockade fence atop the knoll, separating it from a parking lot. No sniper was found.
Howard Brennan, a steamfitter who was sitting across the street from the Texas School Book Depository, notified police that as he watched the motorcade go by, he heard a shot come from above, and looked up to see a man with a rifle make another shot from a corner window on the sixth floor. Brennan gave a description of the shooter, which was broadcast to all Dallas police at 12:45 p.m.
Of the 104 witnesses in Dealey Plaza who are on record with an opinion as to the direction from which the shots came, 54 (51.9%) thought that all shots came from the direction of the Texas School Book Depository, 33 (31.7%) thought that all shots came from the area of the grassy knoll or the Triple Underpass, 9 (8.7%) thought all shots came from a location entirely distinct from the knoll or the Depository, 5 (4.8%) thought they heard shots from two locations, and 3 (2.9%) thought the shots came from a direction consistent with both the knoll and the Depository.
The President's condition was described by staff at Parkland Hospital's Trauma Room 1 as "moribund", meaning that he had no chance of survival upon arriving at the hospital. At 1:00 p.m., CST (19:00 UTC), after all heart activity had ceased and after Father Oscar Huber had administered the last rites, the President was pronounced dead. "We never had any hope of saving his life," one doctor said. Father Huber told The New York Times that the President was already dead by the time he arrived at the hospital, and he had to draw back a sheet covering the President's face to administer the sacrament of Extreme Unction. Kennedy's death was officially announced by White House Acting Press Secretary Malcolm Kilduff at 1:33 p.m. CST.
The ten-month investigation by the Warren Commission concluded that Kennedy was assassinated by Lee Harvey Oswald acting alone and that Jack Ruby acted alone when he killed Oswald before he could stand trial. Many persons believe that this conclusion is contradicted by a film taken by Abraham Zapruder, which suggests that Kennedy's head was struck by a bullet coming from a different direction, perhaps from the "grassy knoll."

Contrary to the Warren Commission, the United States House Select Committee on Assassinations (HSCA) concluded that Kennedy was probably assassinated as a result of a conspiracy. The HSCA found both the original FBI investigation and the Warren Commission Report to be seriously flawed. While agreeing with the Commission that Oswald fired all the shots which caused the wounds to Kennedy and Connally, the HSCA stated that there were at least four shots fired and that there was "...a high probability that two gunmen fired at [the] President." The HSCA did not identify any other person or group involved in the assassination besides Oswald. Kennedy's assassination is still the subject of widespread debate and has spawned numerous conspiracy theories and alternative scenarios.