Grenadier follows the travels of the extremely busty Rushuna Tendo, an expert Senshi, and the samurai Yajiro Kojima, a mercenary swordsman. A Senshi or "Enlightened" is one who is skilled to some degree in the use of guns. The series begins with Yajiro and a small army of samurai launching a frontal assault against a fort in an attempt to free their lord, which was taken over by a group of gunners. The assault fails.
Yajiro orders a retreat, but is spotted by the enemy and chased to a small cliff, which he jumps off of to escape. With his pursuers still following, he follows a nearby hot-water stream upcurrent where he finds Rushuna bathing in a hotspring. She seems undisturbed by his presence or her own nudity and hides him in the hotspring with her ample breasts as cover until the enemy passes them by. After this, she introduces herself as a traveler and reveals the ultimate battle strategy to Yajiro; to avoid battle by removing an enemy's will to fight.
Hearing the gunfire of the renewed assault upon the fort, Yajiro leaves Rushuna to rejoin combat. He arrives in time to see the leader of the gunners use a Gatling Gun to decimate the samurai. Rushuna also arrives at this point and shows her considerable gun talent and effectively ending the battle by defeating the lead gunner and rescuing the lord by herself.
Something in him changing, Yajiro decides to become Rushuna's partner and travel with her.