Mystique is a major antagonist in Super Smash Bros. Crossover starting with Season 17. Mystique is a loyal follower of Magneto, and a major enemy to the heroes. In Season 17, Mystique sees Hal and Jeff being interrogated by Samus Aran, and overhears Hal mention that Samus is a zombie. Mystique tries to help them, but is attacked by Samus and infected in the process. However, she refuses to tell Samus where Ridley and Mother Brain are, but Zombie Sue, who was watching, cut off Mystique's oxygen until Mystique finally talked. After Samus leaves, Mystique is overwhelmed by the virus (humorously, she puked on Hal and coughed her blood on Jeff) and attempts to eat Hal and Jeff, but Zombie Sue tells her to let them go, and brings Mystique to the roof of a tall building where Mystique then watches Naruto Uzumaki, Sasuke Uchiha, Zombie Spider-Man, and Zombie Iron Man battle against the Squadron Supreme as well as Samus attacking Ridley and Mother Brain. Mystique is cured after Samus is defeated.
Mystique's main appearance is based off her standard uniform in the comics. On occasion, Mystique will wear her outfit from the second season of X-Men Evolution onward.
- Despite being loyal to Magneto, Mystique had no problem turning against him and joining Zombie Sue, though this can be attributed to the virus overwhelming her mind.