Portugues, an actress and former professional bodybuilder, filed papers in Los Angeles, citing irreconcilable differences, reported People magazine.
The pair have been separated since March 7, and Portugues is seeking spousal support, according to the divorce filing.
Van Damme, 54, and Portugues have been married for 15 years and have two children.
The actor continues to star in action films, including a "Kickboxer" franchise film that is in post production.
He also made a splash in 2013 with an extraordinary physical feat of doing the splits between two semi trucks.