The 66-year-old singer will star opposite model Arizona Muse in a three-minute film set around a masked ball in Venice as part of the French fashion house's 'L'Invitation au Voyage' campaign.
I'd Rather Be High, one of the tracks from Bowie's first album for 10 years, The Next Day, will provide the soundtrack.
Muse lands in Venice's Piazza San Marco on a hot air balloon and is serenaded by Bowie in a magnificent palazzo.
"David Bowie is an iconic artist," a Louis Vuitton spokesperson told The Times. "He was seduced by the role we asked him to play and by the idea of re-orchestrating the song I'd Rather Be High."
Muse said the identity of her co-star was shrouded in such secrecy that she did not know it was David Bowie until her arrived in Italy for filming.
The advert will be available to view vai an app on November 7 and screened during Homeland on Channel 4 on November 10.
A print campaign in which Bowie will co-star alongside the brand's Vivienne bag (seen below) and Tambour Evolution watch is also planned.