When the French and Indian War broke out, Lignery played an important role in the French defense of the Ohio Country. He distinguished himself in the defeat of Braddock in 1755, in which his company held the French center while Indians and Canadien militia were rallied early in the battle. For his role in the battle he was awarded the Cross of Saint Louis. Given military command of the entire Ohio Country in 1756, he used Fort Duquesne as a base from which to harass British colonial positions in Virginia and Pennsylvania. In 1758 he captured much of a British force led by James Grant that attempted to take Fort Duquesne. Unfortunately, a force he sent out to counterattack the advancing troops of John Forbes was repulsed, and he decided in November 1758 to abandon and destroy Duquesne when it became clear that Forbes' force significantly outnumbered his.