At club level, Preud'homme played for Standard Liège, Mechelen and Benfica. With Mechelen, he won the Belgian Cup in 1987, the Cup Winner's Cup and the European Super Cup in 1988 and the Belgian league title in 1989. He also won the Portuguese Cup with Benfica in 1996. He retired as a player in 1999, aged 40. For Belgium, Preud'homme was capped 58 times, from 1979 to 1995. Other than the 1994 World Cup, he also played in the 1990 tournament.