The cathedral is dedicated to Mary, mother of Jesus under the title of Our Lady of the Assumption.

The parish of St. John the Baptist was established in 1838 and a small frame church building was constructed.

Large numbers of Irish immigrants came to Fall River in the 1840s to work in the mills and they soon overwhelmed the small church.

Bishop John Fitzpatrick of the Diocese of Boston, which covered all of the State of Massachusetts at the time, laid the cornerstone for the present church on August 8, 1852, at the site of St. John the Baptist Church.

[2] When it was time to put on the roof, the old church was dismantled and rebuilt in a near-by location.

In 1901, Bishop Matthew Harkins of Providence consecrated the sanctuary, and in 1904 Pope Pius X named it the cathedral church of the newly founded Diocese of Fall River, its seat first held by Bishop William Stang.

The cathedral is one of several grand Catholic churches built in the city during its heyday as an industrial center, including St. Anne Shrine, Good Shepherd Church (formerly Saint Patrick's), Sacred Heart Church, Espirito Santo, and Saint Joseph's Church, as well as several that have since been lost, including St. Matthieu's in the North End (taken by eminent domain in the 1960s) and Notre Dame de Lourdes in the Flint, which was destroyed in one of the city's most famous conflagrations on May 11, 1982.

St. Mary's Cathedral was designed by prominent Brooklyn, New York church architect Patrick Keely in an “Early English” mode of the Gothic Revival style.

Like the cathedral, it was designed in the Gothic Revival style and its exterior is clad in granite.

The first organ of St. Mary's Cathedral was built in 1952 by George Kilgen & Son of St. Louis Missouri.

Two identical cases were built in the rear of the cathedral with the organ console being placed in the choir loft.

A chamber was added to the north side of the cathedral to house the swell division.