The story is set on the "Planet of Endless Illusion", a place where rogues of all sorts gather. The protagonist, Van, travels the world searching for a man with a clawed right hand who killed his bride. He is joined by several other travelers along the way, each linked to the clawed man by a personal loss.

The series aired on TV Tokyo from July 4, 2005 to December 26 of the same year, totaling 26 episodes. Gun x Sword aired, in English, on Animax Asia in March 2007. The series is licensed for North America by Geneon Entertainment, who produced a new English dub overseen by New Generation Pictures. New Generation's English language version is also available in Australia from Madman Entertainment and in the United Kingdom by MVM Films. At Anime Central 2010, North American anime distributor Funimation Entertainment announced that they have rescued Gun X Sword and re-released the series in late 2010.