As early as 1836, there were Catholics living and working in Holliston with many of them being early Irish immigrants. These people, along with co-religionists from surrounding areas, (Milford, Hopkinton, Medway, Ashland, Upton, Marlborough, Maynard, Westborough, Cordaville, and Saxonville) were visited by Father Tilton of Boston and later by Father Boyce of Worcester. These priests would periodically celebrate Mass in one of the towns. In 1847, Father Boyce, along with Father Gibson, instituted what is known today as St. Mary's Parish in Milford.

In December 1870, Holliston was named a district parish for the Holliston, Medway and Bellingham area. Father Richard Quinlan was appointed as founding pastor. Father Quinlan celebrated his first Mass in Holliston at the Old Meeting House of the Universalist Society. This building previously had been purchased by Father Cuddihy in 1867 and had adapted the worship space to fit Catholic liturgy. However, the Universalist Church was in such disrepair, Father Quinlan sold the building. He began building the present St. Mary's church in 1870, while celebrating Mass in the old Town Hall. The construction of St. Mary's went slowly because Father Quinlan was unwilling to incur a large debt. The first Mass was celebrated in the basement of the new church on Christmas, 1873. The rectory was bought shortly there after. Early in 1883, Archbishop John Williams, with a retinue of priests, came to dedicate the church. It was consecrated to be the home of God under the patronage of Mary.