The single-bullet theory, often derided and discredited by referring to it as the magic-bullet theory, was introduced by the Warren Commission in its investigation of the assassination of U.S. President John F. Kennedy to explain what happened to the bullet that struck Kennedy in the back and exited through his throat. Given the lack of damage to the presidential limousine consistent with it having been struck by a high-velocity bullet, and the fact that Texas Governor John Connally was wounded and was seated on a jumper seat 1+1⁄2 feet (0.5 meters) in front of and slightly to the left of the president, the Commission concluded they were likely struck by the same bullet.

Generally credited to Warren Commission staffer Arlen Specter (later a United States Senator from Pennsylvania), this theory posits that a single bullet, known as "Warren Commission Exhibit 399" (or "CE 399") caused all the wounds to the governor and the non-fatal wounds to the president, which totals up to seven entry/exit wounds in both men.

The theory says that a three-centimeter-long (1.2") copper-jacketed lead-core bullet from a 6.5×52mm Mannlicher–Carcano rifle fired from the sixth floor of the Texas School Book Depository, passed through President Kennedy's neck into Governor Connally's chest, went through his wrist, and embedded itself in Connally's thigh. If so, this bullet traversed 15 layers of clothing, seven layers of skin, and approximately 15 inches of muscle tissue; it also struck a necktie knot, removed 4 inches of rib, and shattered a radius bone. The bullet was found on a gurney in the corridor at Parkland Memorial Hospital after the assassination. The Warren Commission found that this gurney was the one that had carried Governor Connally. This bullet became a key exhibit for the Commission. Its copper jacket was completely intact. While the bullet's nose appeared normal, the tail was compressed laterally on one side.

In its conclusion, the Warren Commission found "persuasive evidence from the experts" that a single bullet caused the President's neck wound and all the wounds found in Governor Connally. It acknowledged that there was a "difference of opinion" among members of the Commission "as to this probability," but stated that the theory was not essential to its conclusions and that all members had no doubt that all shots were fired from the sixth-floor window of the Depository building.

Most pro- and anti-conspiracy theorists believe that the single-bullet theory is essential to the Warren Commission's conclusion that Lee Harvey Oswald acted alone. The reason for this is timing: if, as the Warren Commission found, President Kennedy was wounded some time between frames 210 and 225 of the Zapruder film, and Governor Connally was wounded in the back/chest no later than frame 240, there would not have been enough time between the wounding of the two men for Oswald to have fired two shots from his bolt-action rifle. FBI marksmen, who test-fired the rifle for the Warren Commission, concluded that the "minimum time for getting off two successive well-aimed shots on the rifle is approximately 2 and a quarter seconds" or 41 to 42 Zapruder frames.

The United States House Select Committee on Assassinations published their report in 1979 stating that their "forensic pathology panel's conclusions were consistent with the so-called single bullet theory advanced by the Warren Commission".