1910 in .380acp. Little handgun caused millions of deaths.
Keep this in mind:
That assassination and the resulting diplomatic entanglements let to World War I. WWI involved 20 million dead and 21 million wounded. In Russia, the Bolsheviks used the war as fuel for their revolution, giving communism a solid foothold. In Europe, the eventual armistice sowed the seeds of resentment in Germany, which the National Socialist party used to gain power there, and they helped bring us WWII.
World War II's casualty estimates aren't anywhere near firm, and if you count famine and general trouble caused to civilian populaces, as many as 72 million people were killed. The aftermath of WWII led to the growth of communism and the Cold War, which brought us the wars in Korea and Vietnam. Communism itself racked up an impressive death toll in the far east, as well as revolutionary groups causing mayhem throughout the third world.
The Holocaust so shocked the world that the Jewish state of Israel was created in Palestine, which itself has been the subject of quite a few smaller wars, and which has fueled the anger of Islamic nations toward the West, bringing us modern state sponsored terrorism.
That doesn't even factor in the trouble caused by the superpowers trying to keep up with each other throughout the Cold War, each causing environmental destruction and disease in various places the world over (from assorted cases of spreading poisons in the envrionment).
Think about that the next time somebody says the .380ACP has no stopping power!!! On one hand it is amusing to see what became of that little round, at the same time that amusement is tempered with horror at seeing what became of that shooting. Some shots have lawyers attached. Others will change the face of the globe for centuries to come. If you want a "shot heard round the world," IMO, that one is more influential than any other, including JFK's assassination.