The parish began as "St. Vincent de Paul" and parish records indicate that Mrs. John E. Murphy was influential in the selection of the new name.  The Murphys had generously contributed to the construction costs of the church.

Missionaries ministered to Catholic residents of Harbor Beach and celebrated Mass in homes.  The first congregation was made up of Irish, Polish, German and Scottish immigrants and the first Catholic Church in Harbor Beach (named St. Vincent de Paul) was built in 1882.  Bishop Borgess from the Diocese of Detroit dedicated the church in 1885 and its name was changed to Our Lady of Lake Huron.  In 1899, Father Charles Henigan became its first pastor.  When Father Raymond Fleming arrived in 1912, plans for a new church began.  The old church was moved and work on a new stone and brick church was completed in 1917.  The school was established in 1924 and its last high school graduation was in 1970.  The parish celebrated its 100th anniversary in 1982.

The present church was designed in Tudor Gothic style by Van Leyen & Schilling of Detroit.  The stain-glass windows are a main feature of the building, and these towering windows tell the stories of Mary learning the Scriptures, through the life of Jesus and Mary on earth.  They have served as a tool for catechesis throughout many years, highlighting those truths which are so central to our Catholic faith.

Father Anthony Strauss was assigned as the church's first pastor, and was so well loved it is believed the church was named for his patron saint, St. Anthony of Padua. 

Many of the grandfathers and great-grandfathers of today's parishioners helped in the church's construction.  The great fires of 1871 and 1881 that consumed other churches led to the choice of cement block for the current structure.  Parishioners donated hours of hard labor hoisting block and mortar up to 70 feet in the air in its construction.  In 1911, a 38-inch brass bell cast in Baltimore, with a 65-inch balance wheel was hoisted atop the bell tower. The church's exterior was renovated from 2008 to 2010.