The mountain is located in the Connecticut River Valley of western Massachusetts, and is the namesake of nearby Mount Holyoke College.

Local entrepreneurs John and Frances French were the primary owners; between 1851 and 1900, the hotel and property were subject to a number of upgrades and related construction projects including a covered tramway to the summit of the mountain (first drawn by horse, then mechanized), a railroad from the base of the mountain to a steamboat dock on the Connecticut River, and the construction of a number of outbuildings and trails.

With passenger steamship to the connecting summit railway established, the Mount Holyoke "Prospect House" became a popular tourist destination.

This led to a public outcry and in the mid-1980s the summit house, consisting of the original 1851 structure and the 1861 addition, was restored by the state and through the efforts of local volunteers.

The mountain formed near the end of the Triassic Period with the rifting apart of the North American continent from Africa and Eurasia.

Subsequent faulting and earthquake activity tilted the strata, creating the dramatic cliffs and ridges of Mount Holyoke.

[7] Hot, dry upper slopes, cool, moist ravines, and mineral-rich ledges of basalt talus produce a combination of microclimate ecosystems on the mountain that support plant and animal species uncommon in greater Massachusetts.

[3] Every year in early fall, since 1838, students from nearby Mount Holyoke College participate in Mountain Day.

On that day, at the sound of ringing bells from Abbey Chapel on a random Autumn morning, all classes are cancelled and students hike to the summit of Mount Holyoke.

On May 27, 1944, a B-24 Liberator, flying a night training mission out of Westover Air Force Base in Chicopee, Massachusetts, crashed into a cliff on the side of the range, killing all ten crewmen.

The nearby Connecticut River Oxbow (now a lake), immortalized by the famous landscape painter Thomas Cole just four years before natural flooding and erosion separated it from the Connecticut River, was composed from sketches the artist made from the summit of Mount Holyoke in 1836.