Extreme Hereditary Murphy's Law (EHML) is a condition that affects Milo Murphy and his father Martin. It has been passed down through the Murphy family tree since the term "Murphy's Law" was coined by an ancestor of Milo's, Sheriff Murphy, who lived in 1875.
EHML (commonly referred to simply as "Murphy's Law") is a condition which affects the Murphy family, as well as the main premise of the Milo Murphy's Law series. The basic idea of the hereditary disease is simple: it causes continuous catastrophes among members of the Murphy family. The idea of "bad luck" as seen in the series leads to destructive events. Murphy's Law is shown to have extreme social consequences on whoever has it: most people familiar with the effects of the law will stay away from the afflicted. Despite this, those affected by EHML within the series have a cheerful disposition and a positive outlook.
Most likely, the Murphy's Law "gene" was transmitted for generations until Milo finally received it. Nothing has been stated about how is it transmitted or if there is a way to "catch" EHML other than by birth. Furthermore, it appears that EHML only affects males, which is demonstrated by Sara Murphy, Milo's older sister, being unaffected by it.
As seen in the series, Milo's EHML results in a cyclone of calamities which follows him wherever he goes. This can lead to any kind of consequences, from just slipping to exaggerated catastrophes like entire buildings being destroyed, things catching fire without reason, exploding trucks, etc.
Murphy's Law is unpredictable. The severity of consequences cannot be judged by simply considering the severity of things that have happened before; there is no rhyme or reason to when someone affected will encounter disasters. Therefore, there is no way to "plan" for Murphy's Law except to prepare for any eventuality.
As seen in the show, being affected by Murphy's Law does not negate the possibility of good luck occurring, which is part of the unpredictability of EHML.
Edward Murphy is credited with coining Murphy's Law in our world — the principle that the worst thing can and will happen, and at the worst possible time. However, as Edward Murphy was born in 1918 and died in 1990, so he cannot possibly be the "original Murphy" in the Milo Murphy's Law universe. Milo claims that the original Murphy is his great-great-great-great-grandfather.
In Family Vacation, a scrapbook is shown with many past Murphy family vacations. One is dated 1871. The family were in Chicago during the Chicago fire of 1871. Also, there is a photo dated April 1912 of their voyage aboard the Titanic, as well as one in San Francisco dated 1906 (the great S.F. earthquake).
In The Race, it is revealed that the original Murphy of Murphy's Law was the sheriff of an Old West town that was populated entirely by stranded time-travelers. His EHML had caused all their time machines to break down there. (Cavendish and Dakota even landed there, but they got back to Milo's present by bump-starting their time machine.)