Amanda Seyfried has been cast as the girlfriend of lead character John Bennett, played by Mark Wahlberg.
The same role was taken by Mila Kunis in the first film - which saw her character, Lori, marry John at the end - but she will only have a small role, or will not appear at all in the sequel, according to Deadline.com.
The reason for the change of female lead has been put down to a creative decision by Seth MacFarlane, the movie's creator, who will produce, write and co-star in the sequel as the titular character, a foul-mouthed teddy bear who has been brought to life by John.
'Les Miserables' star Amanda has previously said she will go to great lengths to get film roles, and is not above "begging" for a part she wants.
She said: "Three years ago, a director told me I wasn't made for a certain role and he didn't want to meet me. I called up the casting director and begged him to let me have a trial. I went and he once again told me it was a no.
"I contacted an acting coach, which I never normally do, and went back in a different outfit and did the audition in a different accent, begging them to see me another time. They gave the role to someone else: but it didn't matter, I just wanted to be sure I had done my best.
"It's my biggest strength: not being scared of doing castings that some actresses think they're above. I had five auditions for 'Les Miserables'! Of course, I would never go as far as getting undressed to land a role."