The move — which comes with only two months before the film’s release — has producers scrambling to fill Pacino’s role, Enstarz reports.
Benjamin Bratt — star of television’s Private Practice — has taken over the role and will begin recording his lines shortly.
Pacino, who was to play the villain Eduardo, and the studio cited creative differences for the star’s departure.
“Over the production of Despicable Me 2, there were creative differences between us and Al Pacino … we have mutually decided with Al to replace the voice of Eduardo with a new actor,” the studio said in a release.
Despicable Me — which, like the sequel, stars Steve Carrell — earned more than $500 million in 2010.