The story, about an enforcer for a criminal syndicate who, with his son, has to go on the run from his bosses, is a fictional one although it is largely inspired by similar events in real life. It is based on a graphic novel by the US thriller writer Max Allan Collins and published in 1998.  This novel became the first of a series, all with quite similar titles: On the Road to Perdition, Road to Purgatory, Road to Paradise and Return to Perdition. The graphic novel itself was based on another story, a Japanese manga series which translates as Lone Wolf and Cub. This series started in 1970 and is quite different from Road to Perdition, but has the same basic story of a man who has to flee from his dangerous bosses accompanied by his young son. In fact, an American remake of a Japanese film version of this story is also planned, so altogether it has had a lot of international influence.

So Road to Perdition has its origins in fiction. However, it is set in the US Great Depression of the 1930s and several real-life historical people appear or are mentioned in the film, and there are incidents which are inspired by real life. Most importantly, the main character Michael O’Sullivan’s conflict with his boss is similar to a fight that a real life gang leader, John Patrick Looney, had with one of his own associates, as a result of which the associate’s son was killed.

Looney was every bit as dangerous as the similarly named John Rooney, and like him he operated in Rock Island, Illinois. He basically owned the whole area; he even had his own newspaper which printed only stories favourable to him and attacking (often even threatening ) his many enemies. He was actually a well educated man who studied law and even considered a political career before becoming a full time gangster (he was involved in shady dealings early on). In fact, a major reason why he started the newspaper was that he thought the existing Rock Island newspaper was biased against  him. He was finally caught in 1922, so his reign was earlier than the Depression period (Sam Mendes’ film actually opens in 1931).

Just in case you haven’t seen the film, this paragraph contains spoilers! Like Rooney in the film, Looney had a son called Connor, who was killed in Rock Island in 1921 during a fight with a rival gang. Connor is also killed in the film, though this is part of Michael O’Sullivan’s personal revenge on the family rather than a gang attack. And in the film, O’Sullivan also kills Rooney before being killed himself. The real life Looney had a less dramatic end: he served 8 years in prison for the only murder that was ever actually pinned on him (though certainly not the only one he ever committed) and after his release lived a quiet life for another 13 years before dying of TB in Texas.

Another way in which Road to Perdition is based on fact is in its portrayal of the background of the Great Depression. Even though, as said, Looney’s career was over before the Depression started, and in fact the gang culture had probably already reached its peak with the terrible St Valentine’s Day Massacre in 1929, organised crime continued to flourish during the Depression years of the 1930s and many people were involved with or committed desperate deeds. The film makes it clear that this was a violent and dangerous era when ‘mob justice’ was common.

You can read more about the film's real-life background here.