The world is invaded by "Minus Waves", which are created by the mixing of scientific research and magic in an attempt to resurrect an ancient, powerful and evil god named Gyumao.

Goddess Kanzeon sends the Buddhist monk Genjo Sanzo and his acolytes Son Goku, Sha Gojyo, and Cho Hakkai to Tenjiku (India) to stop the curse and prevent Gyumao's resurrection.

[6] in North America AEsir Holdings licensed the anime, released the series as part of a complete collection of Saiyuki on DVD in February 2013 and April 2015, and on Blu-ray in March 2019.

[21] In September 2005, Japanese television network TV Asahi broadcast a popularity poll based on a nationwide survey in which Saiyuki was placed 96th of the channel's Top 100 Anime.

[28] Writing for Anime News Network (ANN), Bamboo Dong said he found "the adventures of Sanzo Group with random people/objects and the concept of redoing the classic Chinese myth with modern day equipment" to be interesting, and called Kazuya Minkura's story "creative".

[33][34] Lien-Cooper, reviewing Saiyuki Volume 6: Demon Rising, graded it 8 out of 10 and praised the "interesting plots with varying tones (funny, scary, tragic), some unexpected twists and turns, and especially the characters".

[35] Fellow Sequential Tart reviewer Sheena McNeil gave a 9-out-of-10 grade to first volume, and praised the art and animation, which has "some new styles of overlapped frames and use of static like shading".

McNeil said the story "is definitely a new twist on the relationship between humans and demons as they normally get along peacefully ... [and] also combines a quest with a "Good vs Evil" battle"; and called the themes and characters "diverse".

[39] In her review of the tenth volume, Dozier called its animation "glossy and gorgeous", and the fight scenes "cutting-edge", but she found connecting with the main characters difficult.