- 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 克格'莫的 Icathian Surprise, 约里克的Omen of Death Omen of Death and 婕拉的 Rise of the Thorns.
- 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 Death Note.
- 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 World of Warcraft, 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 Statue of Liberty in New York City.
- Grim Reaper Karthus has the scythe that Death 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.
- Phantom Karthus is most likely a reference to the Phantom of the Opera, due to the mask on the left side of his face.
- 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".