Beginning in the 1850s, Williamston Catholics worshipped with visiting priests. They often traveled ten miles by carriage or horseback on rutted, muddy roads to Saint Patrick Church in Woodhull (present-day Shaftsburg) to worship with Father Louis Van Den Driessche (Van Driss) of Lansing. In 1866 two brothers, Jerome and James Waldo, entered into a contract with Detroit Bishop Peter Paul Lefevere, stipulating they would sell a plot of land in the village of Williamston to the diocese for twenty-five cents, provided that a church worth at least one thousand dollars was built within three years. In 1869 a frame church costing eleven hundred dollars was erected on this site and named Saint Mary. Father John Lovett became the first resident pastor in 1879. Descendants of Saint Mary's founding families continue to worship here.
During the winter of 1868-69, Owen Brannan and Peter Zimmer cut and hauled timber to construct the first of three Catholic churches on this site. Saint Mary Church became a parish in 1879, upon the arrival of the first resident pastor. From 1889 to 1898, despite its growing membership, the parish did not have a full-time priest and it became a mission. In 1895 the church burned. A larger, brick, Neo-Gothic building was erected the same year. Under the leadership of Father John J. Connolly, who served from 1898 to 1905, Saint Mary regained parish status. It comprised the church; a cemetery, founded in 1873; and a new rectory, erected in 1902. In 1948 a parish hall was built. In 1956 a convent was established for the Sisters of Saint Joseph who staffed the school that opened in 1959. The present church was built in 1985.