As part of the 2013 Glasgow Film Festival, the cathedral will become the venue for a rare showing of The Passion of Joan of Arc, a silent film from 1928.
The screening of the film by Carl Dreyer will be the first ever public feature film screening at the landmark building noted for its Gothic architecture.
The temporary screen will be joined by live music, with an electronic score for organ, electronics and soprano by composer Irene Buckley.
The event will take place on February 23 as part of the annual film festival, which has staged unusual screenings before.
Last year the festival included a screening of the 1954 Ealing comedy The Maggie on board the tall ship The Glenlee, and in 2011 the "wet sounds" event asked patrons to don swimming costumes and goggles to see underwater projections.
The festival also recently announced a Calamity Jane screening and barn dance at the Grand Ole Opry Western-themed club for the film festival 2013.
Allison Gardner, festival co-director, said: "We can't think of a more beautiful or appropriate setting for this masterpiece of cinema art. It's a stunning film; it looks like nothing else in cinema history and it's cemented by one of the best leading performances of all time.
"Irene Buckley's score and the atmospheric surroundings of Glasgow Cathedral are going to make this a completely unique experience for all the senses.
"And this is just the tip of the iceberg. We'll be announcing more exciting Glasgow Film Festival events in completely new locations around the city in the new year."
In the movie, Joan is accused of heresy and witchcraft, and the saint endures "the taunting and deceit of the English-backed church court," the festival said.
"It is only through her faith that she can rise above her tormentors. Dreyer's masterpiece is a visual hymn to the triumph of the soul over life."
The ninth Glasgow Film Festival runs from February 14 to 24, with the full programme launched on January 16 and tickets on sale from January 1.
One of the films that has used Glasgow Cathedral as a setting is Death Watch, the 1980 sci-fi drama starring Harvey Keitel and directed by Bertrand Tavernier, the remastered print of which premiered at Glasgow Film Festival 2012.
The Passion of Joan of Arc stars Renee Jeanne Falconetti as Joan, in her only cinema performance. Jean Cocteau said of the film: "It seems like an historical document from an era in which cinema didn't exist."