Wilson was due to voice Mei Mei, a crazy ribbon-dancing panda (the movie series' first female panda lead), who is romantically obsessed with Po.
Insiders say the production schedule became extended, forcing Wilson to bow out, said The Hollywood Reporter.
Jack Black, Angelina Jolie, Seth Rogen and Dustin Hoffman are among those reprising their roles in the hit franchise telling the tales of Po, the noddle-peddling panda who is also a fabled Dragon Warrior.
Oscar-winner JK Simmons and Bryan Cranston are among the new additions to the cast.
Jennifer Yuh Nelson and Alessandro Carloni are directing the movie, which has a release date of January 29, 2016.
The new storyline sees Po reunited with this long-lost father and he discovers a long-lost panda paradise.
His newfound happiness is threatened with the emergence of a supernatural villain (Simmons), Po has to go from student to teacher as he must train a village of bears to master the martial arts.
This is the first animated voice work for Hudson, who is currently shooting "Mother's Day" for Garry Marshall.
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