The character was featured in 1970s cartoons by the underground cartoonists Dave Sheridan and Fred Schrier, appearing in person in the early 1970s on Rowan & Martin's Laugh-In and later in the 1975 The Smothers Brothers Comedy Hour.

In the late 1970s, Father Guido Sarducci was featured on radio commercials for High Times magazine, where he offered to perform blessings for a fee.

Most of his appearances on SNL have been on Weekend Update, including one where he reported that "The take at the shrines in Italy has gone down", which he suggested correcting by creating "Shrinemobiles" and thus taking the shrines to where the people were, and another where he is sent to London to try to wake up Paul McCartney at 4:30 in the morning (11:30 in New York) by throwing coins, obnoxiously singing The Beatles and Wings songs, and finally, throwing a rock at the window—he says it works every time.

In 1981 Novello made newspaper headlines when he visited Vatican City wearing the Father Guido Sarducci costume to do a photo shoot for Time magazine.

After taking pictures in an area where photography was prohibited, he and his photographer, Paul Solomon, were arrested by the Papal Swiss Guards and Novello was charged with "impersonating a priest".

The same movie featured a cameo by his fellow SNL alumnus Dan Aykroyd as the Ghostbuster Ray Stantz.

In the 2001 Disney animated film Atlantis: The Lost Empire, Novello uses the voice and speech style of Father Sarducci to portray the character of demolitions expert Vinny Santorini.