Prior to the arrival of English settlers in the early 18th century Native Americans of the Mahican Tribe hunted and traveled throughout the Greylock area. Most notably, what is called the Mohawk Trail today, passing beneath the northern flank of the mountain along the Hoosic River, was a traditional footpath for trade and war between the Hudson and Connecticut River Valley tribes.

Fall snow on Mount Greylock inspired Herman Melville's description of the white whale breaching the waves in "Moby Dick"

In 1739 Ephraim Williams Sr., father of the founder of Williams College, led a survey party and laid out two townships boundaries over and around Greylock, later incorporated as Williamstown and Adams. Increasing conflict between France and England for control of western New England led to the construction of a series of fortifications along the Massachusetts Bay Colony’s northern boundary, including Fort Massachusetts at present day North Adams.  It wasn’t until the cease of hostilities from the French and Indian Wars that settlement began in earnest. About the 1760s the open farmland and pastures of settler farmers crept higher up the rugged slopes of the mountain. Small industries around the base of the mountain soon followed. Saw and grist mills utilized the abundant water runoff for power. During this period the name of the “Hopper” valley gained its name in resemblance to a grist mill’s grain hopper.

Early names for the mountain included Grand Hoosuck and Saddleback Mountain. Around the 1830s the “Graylock” name came into popular use; its origin, like the summit, is cloudy. Perhaps in poetic reference to its cloud-wrapped or frosted wintertime appearance, or the legendary Western Abenaki chief, Wawanolet, whose raids into the Massachusetts Bay Colony c.1722-27 caused fear and respect.