Castagne began his career with Virton, where he made his professional debut in 1995. In 1997, he moved to Anderlecht, where he won three Belgian Pro League titles and two Belgian Cups. In 2004, he joined Milan, where he won the Serie A title in 2004 and the UEFA Champions League in 2007.
Castagne made his international debut for Belgium in 1999. He went on to make 54 appearances for his country, scoring four goals. He represented Belgium at the 2002 FIFA World Cup and the 2000 UEFA European Championship.
After retiring from football in 2008, Castagne worked as a pundit for Belgian television and radio. He is also a successful businessman, having founded several companies.
In 2021, Castagne was inducted into the Belgian Football Hall of Fame.