In his autobiography Beginning, Kenneth Branagh says that he was one of the finalists for the role of Mozart, but was dropped from consideration when Forman decided to make the film with an American cast. Hulce reportedly used John McEnroe's mood swings as a source of inspiration for his portrayal of Mozart's unpredictable genius.
Meg Tilly was cast as Mozart's wife Constanze, but she tore a ligament in her leg the day before shooting started. She was replaced by Elizabeth Berridge. Simon Callow, who played Mozart in the original London stage production of Amadeus, was cast as Emanuel Schikaneder, the librettist of The Magic Flute.
The film was shot on location in Prague, Kroměříž and Vienna. Notably, Forman was able to shoot scenes in the Count Nostitz Theatre in Prague, where Don Giovanni and La clemenza di Tito debuted two centuries before. Several other scenes were shot at the Barrandov Studios.
Forman collaborated with American choreographer, Twyla Tharp.