The film, which also stars Michael Cera and Catherine Keener, was scheduled to begin production September 26 in and around Cartegena, Colombia, said The Hollywood Reporter.
49-year-old Ferrell's last-second exit has left director Sebastian Silva and the producers scrambling. Several of the cast and crew already are in Colombia awaiting word on the project's future.
In a twist of life imitating art, "Captain Dad" chronicles a family vacation gone awry when the plans break down. Silva also wrote the screenplay.
It is unclear if producers Anne Carey, Bingo Gubelmann, Benji Kohn and Austin Stark can get the film back on track given the prominence of Ferrell's character (he plays the titular dad).