- Ascended Fanon: Before the manga was adapted into anime, Minekura wrote up a character profile for the four main characters and jokingly "assigned" Hakkai Akira Ishida as his voice actor. Once the adaptation is made, guess who actually gets the job to voice Hakkai?
- Decomposite Character: Akin to another Sun Wukong/Son Gokuu, the one in this manga shares the original Zhu Bajie/Cho Hakkai's hunger from Journey to the West, while the Saiyuki Wujing/Gojou has both the "lust for women" part and "fights with Wukong/Gokuu" part.
- The Other Darrin: Like you wouldn't believe.
- Even before the infamous English cast switch between ADV and Geneon from the first and sequel series, some actors would change in the first two seasons. Dokugakuji changed near the end of the first season from Jason Miesse to Mike MacRae and Shawn Taylor replaced Karen Coffer as the Merciful Goddess for three episodes as well. The difference for the latter was more noticeable than most since Taylor used a strong English accent that Coffer lacked.
- Dr. Huang was voiced by Kelli Cousins (who also provided the vocals for Hakuryu) up until episode 29. She was replaced by Rozie Curtis for her last number of episodes in Season 2.
- Averted in the movie for the most part, except for Kanan where Sasha Paysinger replaced Allison Keith in the role.
- Even minor and unnamed characters would fall prey to this. The Fake Hakkai was voiced by John Swasey in Season 1 before Mike Vance replaced him for reasons unknown (John was still voicing Filler Villain Zenon at the time). Also, the Merciful Goddess' messenger Egan was voiced by Jarrod Huffaker before being replaced with Adam Conlon.
- Geneon's dub of the sequel series was mostly consistent except for a few cases:
- Cindy Robinson replaced M.A. Lovestadt as Lirin in Gunlock. The change was rather subtle that less trained ears never noticed the difference.
- Kirk Thornton replaced Steve Kramer briefly as Jiroshin at the end of Reload; Kramer would return for his remaining appearances in Gunlock.
- A rather odd case of this would be young Sanzo/Koryuu. He was voiced by Mona Marshall in some early filler episodes, but later during the God arc the voice is done by Mela Lee (who primarily voiced Yaone). Instead, Marshall is now voicing the titular God as a child, meaning that she is basically talking the child version of a character she had previously recorded for in the same season. Confusing, right? It comes full circle in Gunlock where Marshall is back to voicing young Sanzo. All in all a rather strange choice since Lee could have just as easily voiced young God instead.
- In the Gaiden OVA, while Sentai Filmworks was able to regain all of the original four leads, all secondary characters were recast, most likely due to them either retiring/being unavailable. Karen Coffer was replaced with Shelley Calene-Black as the Merciful Goddess (she'd previously voiced Yaone, who didn't make an appearance in the OVA anyway). It continued with Leraldo Anzaldua replacing Jason Konopisos as Gojun, John Swasey (Zenon) replacing Ben Pronsky as Li Toten as well as Todd Waite as Jiroshin, and Clint Beckham replacing Tony Oller as Nataku (the last of these being justified since the original actor had long since gone through puberty). The Japanese version also had this, with Hiroki Tochi replacing Kazuhiro Yamaji as Gojun and Minoru Inaba replacing Tsutomu Isobe as Toten
- The Japanese side was no less immune to this trope, as the original OVAs had a completely separate cast from the TV series. Wataru Takagi was Sanzo, Kosuke Okano was Goku, Kōichi Yamadera was Gojyo, Yuki Matsuda was Kougaiji, Tomoko Ishimura was Yaone, Yumi Touma was Gyokumen, Masashi Sugawara was Dokugakuji, and Sakura Nogawa was Lirin. They would be replaced by Toshihiko Seki, Soichiro Hoshi, Hiroaki Hirata, Takeshi Kusao, Yuko Minaguchi, Shinobu Sato, Dai Matsumoto, and Kaoru Morota respectively. Only Akira Ishida would reprise his role as Hakkai in the TV series. Controversially, Minekura stated in an interview that enjoyed Yamadera's performance as Gojyo better. (Though she also wrote in one of the artbooks that she "likes him so much it vexes" her.)
- In Reload and Gunlock, there would be more recasts, with Jurota Kosugi replacing Matsumoto as Dokugakuji and the late Tomoko Kawakami replacing Morota as Lirin. Rei Igarashi would take over for Misa Watanabe as the Merciful Goddess and Mitsuru Miyamoto would replace Ken Narita as Koumyou Sanzo.
- A peculiar version goes to Hakuryu, who was voiced by Kaoru Morota in the original seasons (also Lirin). The vocal effects were provided on and off by Tae Okajima and Eisuke Kotanizawa in Reload, but in Gunlock, only Okajima provided the voice. The Japanese effects were retained in the English dub as opposed to letting an English actor/actress redo them, like ADV's Kelli Cousins.
- Another minor change was Kahoru Sasajima taking over Yuko Kobayashi as Koryuu and Masayo Hosono replacing Kayu Suzuki as young Gojyo.
- Reload Blast has David Matranga, Greg Ayres, and Vic Mignogna reprising their roles as Sanzo, Goku, and Kougaiji respectively, however Hakkai is now voiced by Micah Solusod (as Braden Hunt hasn't done anything since 2011) and due to the 2014 controversy that pretty much ended Illich Guardiola's career, Gojyo is now voiced by Ian Sinclair, and also voices his previous incarnation Kenren.
- Dokugakuji was recast on both fronts yet again with Jin Yamanoi replacing Jurota Kosugi and Josh Grelle replacing Mike MacRae. Kosugi has gotten too expensive and MacRae has mostly moved on from voicing in anime.
- Schedule Slip: The series has been running since 1997 but has yet to be completed and has gone on Hiatus many times due to 1. author Kazuya Minekura is also doing another manga titled Wild Adapter and 2. her ill health which lead to her having a hysterectomy and a jaw operation to remove a tumor on her right upper jawbone!
- What Could Have Been: Vic Mignogna was initially called in to audition for (and more than likely be casted for) Gojyo in the dub for Gensoumaden, but he backed down from the offer because of Gojyo's excessive use of profanity, so he instead auditioned and was cast to play Kougaiji.
- The original title for Gensoumaden in the dub, was going to be called "Paradise Raiders," but they decided to keep it as Saiyuki.
Trivia / Saiyuki