When the Americans invaded Quebec in 1775, Pélissier, whom his business associate Pierre de Sales Laterrière described as a "strong supporter of John Wilkes and his system of freedom", strongly supported the American cause.

General Richard Montgomery met with him in December 1775 to discuss the establishment of a provincial convention for the purpose of electing representatives to the Second Continental Congress, a step Pélissier advised against until Quebec City was taken.

On July 29, 1776, he received an engineering lieutenant colonel's commission in the Continental Army, and in October assisted in the improvement of the defenses at Fort Ticonderoga.

[3] When he fled Quebec, Pélissier left behind his second wife Catherine, who began to have an affair with Laterrière in his absence.

Pélissier, apparently unaware of the affair, was eventually granted permission to return to Quebec to bring her to France.