It was the deadliest terror attack in the city until 9/11.
Nearly 100 years later, the case remains unsolved -- and it's not the only high-profile attack that investigators never unraveled.
A horse cart exploded in front of J.P. Morgan's headquarters on Wall Street, blasting metal shrapnel and shattering blocks of windows.
"Almost in front of the steps leading up to the Morgan bank was the mutilated body of a man," wrote reporter George Weston. "Other bodies, most of them silent in death, lay nearby. As I gazed horror stricken at the site, one of these forms, half-naked and seared with burns, started to rise. It struggled, then toppled and fell lifeless into the gutter."
New York police, the Secret Service and the Bureau of Investigation (which preceded the FBI) tried to figure out who was responsible, but came up with few leads.
Letters from the "American Anarchist Fighters" were found in the area before the bombing, and they seemed similar to ones from two earlier bombings connected to Italian anarchists.
"The best evidence and analysis since that fateful day of September 16, 1920, suggests that the Bureau's initial thought was correct—that a small group of Italian Anarchists were to blame," a modern FBI summary concludes. "But the mystery remains."
Shrapnel still scars the nearby buildings today.
1933: The first airplane bombing, over Indiana
The first-known sabotage of a plane remains unsolved to this day.
On October 10, 1933, a United Airlines Boeing 247 flying from Newark to Cleveland and then on to Chicago exploded over Chesterton, Indiana. All seven people on board were killed.
Headlines across the country noted the "giant" plane going up in flames.
"Consolidation of all available evidence surrounding the accident leads to the conclusion that it was caused by a high explosive, presumably located in the area of the cargo space and toilet section, aft of the passenger cabin," United Air Lines Vice President D.B. Colyer told the New York Times.
Leads ranging from labor disputes to New York or Chicago mob actions were suggested, but the Bureau of Investigation never solved the case. J. Edgar Hoover ordered it closed in 1935.
1940: World's Fair, NYC
The New York World's Fair was packed on July 4, 1940 when a ticking suitcase was discovered inside the British Pavilion.
The canvas bag was moved to a nearby area where two New York detectives attempted to defuse it. The bomb went off, killing Joseph Lynch and Ferdinand Socha and injuring five other police officers.
According to reports at the time, police questioned German Bund members, Italians and Communists.
"All known radicals in the metropolitan area were rounded up today as police made an unprecedented effort to track down those responsible..." the Associated Press reported the next day.
Despite the search, no one was ever held responsible.
1975: LaGuardia Airport, NYC
It was the Monday after Christmas 1975 when a bomb tore through the TWA baggage claim at New York's LaGuardia airport. The explosives, thought to be equivalent to 25 sticks of dynamite, killed 11 and injured 74.
Authorities did have leads. Nine months later, a TWA plane leaving LaGuardia was hijacked by Croatian nationalists who left a bomb in a locker in Grand Central Station. The two bombs seemed to match, but the hijackers denied responsibility for the LaGuardia bombing even after they were released from prison more than three decades later.
Despite one of the biggest New York Police Department investigations ever, no one has ever been arrested for the airport bombing.
1984: Heathrow Airport, London
A bomb tore through the unclaimed baggage section of Heathrow Airport on April 21, 1984, injuring 25 people.
Authorities investigated links to earlier bombs planted by Libyan groups, and a plane from Tripoli had landed four hours before the attack. A few days earlier, British police were engaged in a standoff at the Libyan embassy after someone inside fired a machine gun at protesters.
Separately, an anarchist group claimed responsibility for the attack. However, in the end, no one was ever arrested.
2008: Times Square, NYC
Despite modern techniques and even surveillance video
, the bomber who targeted Times Square in 2008 remains at large.
The blast went off early in the morning on March 6 in front of the Armed Forces Recruiting station.
The FBI says the suspect rode a blue bicycle, placed an ammunition can with the bomb inside, lit a fuse and left. No one was hurt.
Investigators believe as many as five people could have been involved. The bombing could also be connected to one at the British Consulate in 2005 and another at the Mexican Consulate in 2007.
The FBI and the NYPD are still offering a $115,000 reward for information leading to an arrest.