The Catholic League took out the newspaper advert as NBC is set to launch the comedy, called The Real O'Neals, tonight.
The Real O'Neals is based on the life of Dan Savage, a gay rights activist who has been outspoken against politicians and the Church for holding conservative views on homosexuality, as well as the LGBT establishment.
The sitcom will feature a close-knit Catholic family in Chicago - one similar to that which Mr Savage grew up in himself.
The Catholic League said in the advert: "For those not acquainted with him, his maniacal hatred of Catholicism is so strong that it would be as though David Duke [a former Ku Klux Klan Grand Wizard] were hired to produce a show about African Americans.
"Savage has accused a politician of having sex-he used an obscenity-with the consecrated Host, the body and blood of Jesus. His filthy remarks about Jesus and Our Blessed Mother are so over the top that they would make Larry Flynt [a sexual magazine publisher] blush.
"Pope Benedict XVI, Pope John Paul II, and Cardinal Francis George are portrayed as perverts.
"And priests - he indicts all priests - are depicted as predators."
Dan Savage is an executive producer of The Real O'Neals, but did not write the programme.
Mr Savage also writes a column on love, sex and relationships, has authored several books, and founded a charity dedicated to reducing the number of gay people committing suicide.
He has openly supported internet pornography.