Anson Mount played the video game Red Dead Redemption for about a month before his audition, and he has been often told that his character bears resemblance to John Marston, the protagonist of the game.

In the 5 seasons of the show, no actor appeared in every episode.

The series portrays the events affecting the real-life characters and their actions, namely Thomas Durant, Collis Huntington, Brigham Young and Ulysses Grant with historical accuracy. Many of the schemes employed by Thomas Durant throughout the series, including manipulating stock prices in the first two seasons and misleading land investors in the fourth and fifth season actually occurred.

Eva is loosely based on Olive Oatman who was also captured by Native Americans, bore the exact facial tattoo and re-assimilated back into white society.

Thor Gundersen was always referred to as "The Swede" yet he always insisted, "I am Norwegian.". However, at the time this story takes place, Norway was under the Swedish crown, and had been since 1814. So his immigration papers would have had him coming from Sweden/Norway. Norway had its own Constitution, seperate from the Swedish, but did not become independent until 1905. As many Norwegians wanted independence, it is very plausible for Gundersen to consider himself Norwegian instead of Swedish.

As a result of attacks by Native Americans, the US Army had to accompany the mobile "town" that followed the railroad crews as the Union Pacific moved west. These towns were mostly tents and wagons and not only consisted of the railroad workers, but entrepreneurs who provided services to the workers such as gambling and prostitution. "Hell on Wheels" was the actual name of the mobile tent community at that time. It was originally coined by the newspaper editor of the Springfield Republican newspaper and the name stuck.

Christopher Heyerdahl and Colm Meaney were also primary antagonists on Stargate: Atlantis (2004) (Todd the Wraith and Cowan of the Genii, respectively).

David Von Ancken directed the first and last episode of the show.

Thomas Durant is frequently referred to as the "old man" throughout the series, but in reality he was in his late 40's and 49 when the golden spike was placed at Promontory Point in Utah. Colm Meaney on the other hand who played Thomas Durant was 58 years old in Season 1 and 63 years old in Season 5.

The character of Cullen Bohannon was loosely based on former Union General John "Jack" Casement, the real life chief engineer for the Union Pacific hired by Thomas Durant. He was later replaced by Major General Grenville Dodge but kept on as chief construction "boss" much the way Thomas Durant hired a chief engineer in season 2 but kept Cullen Bohannon on as chief construction "boss".

John Campbell was the first territorial governor of Wyoming and was appointed to two terms by President Grant. He was first appointed territorial governor in 1869, the same year the transcontinental railroad was completed. In the series it is depicted that he becomes governor in 1868. Also, he turned 34 years old in 1869. The actor who portrays him, Jake Weber, was 50 years old when he first appeared in Season 4, six years older than the real John Campbell when he died at age 44.

"Hell On Wheels Main Title" Written by 'Kevin Kiner' and 'Gustavo Santaolalla'

Features Wes Studi, Tom Noonan, and Ted Levine. All of whom appeared in Heat together, and are regulars of Michael Mann films.