Aboard the Advenna Avis in 1711, a group of alchemists summon a demon in the hopes of gaining eternal life. The demon gives them an elixir of immortality and the method of ending their existence by "devouring" one another. Soon after, one among them begins to devour his companions. Realizing the danger posed by staying together, they scatter across the globe.

Centuries later in 1930's America, a certain federal investigator tries his best to combat the rise of organized crime during Prohibition, send a particularly infuriating terrorist to Alcatraz, and catch an outrageous thief duo. Meanwhile, the transcontinental train, the Flying Pussyfoot, begins its trail of blood across the country.

In 2002, a small group of the original Advenna Avis alchemists are on a journey to find the rest of their fellow immortals. However, there is one companion they did not expect to meet again.

Seemingly unrelated events, from a sleepy Italian city in the early 1700's to a modern luxury cruise ship traveling across the Pacific, reveal themselves to be far more connected than anyone could imagine...

Baccano! was simultaneously published in English by Yen Press on the same day as the Japanese release. It was published in print from January 30, 2018 to May 22, 2018.