The 26-year-old winger came off in tears in her club's 1-0 win over Paris Saint-Germain last weekend that saw them clinch the French title. Lyon said that tests revealed a "partial rupture of the right anterior cruciate ligament" and confirmed she would require surgery.
The news is a major blow to fifth-ranked France's hopes of making an impact at the World Cup under new coach Herve Renard. They are already set to be without striker Marie-Antoinette Katoto as she recovers from a long-term injury.
Cascarino is the latest in a long line of top female players to suffer such a serious knee injury. Key United States midfielder Catarino Macario, also of Lyon, was ruled out of the World Cup earlier this week with a similar problem.
England captain Leah Williamson also recently saw her hopes of featuring at the tournament ended by a knee injury. Spain's Alexia Putellas, the reigning women's Ballon d'Or, has spent the last nine months out with a knee injury of her own, but is hoping to be fit in time to travel to the World Cup.