The 90-minute one-off programme, titled Worried About the Boy, has been written by Hotel Babylon's Tony Basgallop and will be directed by Julian Jarrold, who worked on Red Riding.
The drama will follow George's rise to fame and will chronicle his life from falling in love for the first time to embracing his style and meeting his Culture Club bandmates.
Newcomer Douglas Booth will play Boy George, Gavin & Stacey star Horne has been cast as Culture Club drummer Jon Moss, and Gatiss will portray music impresario Malcolm McLaren.
Hustle's Marc Warren has also signed up to play nightclub pioneer and Visage frontman Steve Strange.
"Worried About the Boy will be an evocative and visually enticing drama about one of our most iconic British pop stars," said the BBC's Ben Stephenson.
"With its mix of music, fashion and youth, it rounds off our trio of dramas for BBC Two's '80s season perfectly."
Worried About the Boy begins filming in Manchester later this month.