- Karthus is one of five champions voiced by Adam Harrington, the other four being Kassadin, Mordekaiser, Ryze, and Shaco.
- Karthus' ultimate, Requiem, has the same name as the Catholic gathering called the "Requiem Mass", which is dedicated to praying for the souls of the deceased.
- The old icon for Karthus' passive, Death Defied was a sheep.
- Karthus is one of the four champions to have abilities which allow them to continue to attack after death. Karthus's ability being Death Defied and the others being Kog'Maw's Icathian Surprise, Yorick's Omen of Death and Zyra's Rise of the Thorns.
- There is a glass case which has "Press R to Win"" in all caps in the video of the Mac Version Launch which possibly references people playing as Karthus stating Press R to Win.
- Karthus is possibly inspired by the Four Horsemen of the Apocalypse, particularly the rider symbolizing Famine.(The other horsemen theme champions to have been released so far are, Thresh, Morderkaiser, and Hecarim.)
- Karthus shares the quote with Evelynn: "Their pain is my pleasure".
- Karthus quote "I will put you...In my book." may be a reference to the anime .
- In Karthus' Chinese splash artworks, he does not have a skull face. This is likely because the use of exposed bones in video-games is explicitly forbidden in China (a famous example is the race Undead in  , where in the American server their bones are exposed, while in the Chinese server they're covered).
- The Statue of Karthus is a reference to the in .
- Grim Reaper Karthus has the scythe that
is usually depicted to be wielding rather than his usual staff.
- The book he is holding in Grim Reaper skin it is known as the "Necronomicon" a fictional book of the dead, attributed to the works of H.P. Lovecraft.
- Phantom Karthus is most likely a reference to the Phantom of the Opera, due to the mask on the left side of his face.
- Pentakill Karthus seems to have a drinking problem, as seen here.
- In the classic skin's splash artwork and model, Karthus is holding a book with the League of Legends icon on it's cover, only with a few alterations.
- Karthus originally was a self-appointed Over-lord of Howling Marsh before his lore changed into being working for Shadow Isles.
- Karthus is the fourth member of the famous Pentakill band with Mordekaiser, Sona, Yorick and Olaf. Karthus takes the role of Lead Singer as Pentakill Karthus, "the Deathsinger".
- Karthus was present in a fight between Malzahar and Kassadin. He was found "dead" at the scene, but he was revived since then. He stated that he was "protecting the inhibitor," referring to something other than the inhibitors on the Fields of Justice.The Journal of Justice: Volume 1, Issue 21