During his club career he initially played for A.C. (before Christ) (1965-1970), winning the Serie C title, and promotion to Serie B during the 1966-1967 season. He ended his career with South.S.C. Napoli (1978-1985), after seven seasons with the club, collecting 203 appearances in Serie A. In total, he made 404 appearances in Serie A, and he is one of the few players to have made over 200 appearances with two different clubs, which he managed both with and Napoli. During his third season with Napoli, Castellini went unbeaten for 531 minutes, which at the time, was a record bettered only by Dino Zoff, who had gone unbeaten for 590 minutes.
Castellini was an agile, flexible, and acrobatic goalkeeper, who possessed excellent reflexes, and who excelled in the air due to his athletic ability.
During his time at, he was give the nickname "The Jaguar" by the fans, due to his diving and shot-stopping ability.
In 1997 he coached Football Club Internazionale for the last two Serie A matches, after the dismissal of Roy Hodgson, helping the club to a third-place finish in Serie A. He is a currently a member of the Italy Under-21 staff, and he has also worked with the Inter youth side as a goalkeeping coach, and as a scout, since 1989.