Carlo Gaetano Samuele Mazzuchelli was born November 4, 1806 in Milan, Italy, the 16th of 17 children, though only a handful of his siblings survived past childhood. He was educated at a boarding school in Switzerland, and at age 17, he decided to join the Dominican friars, at a time when the order was suffering from the effects of the French Revolution. During his studies, he heard the pleas of Bishop Edward Fenwick of Cincinnati, himself a Dominican, who begged for priests to serve in the remote stretches of his diocese where Catholics did not have a priest to minister to them. Brother Samuel requested to be assigned to this mission territory, and in 1828, he set sail for America. He completed his studies for the priesthood and was ordained in Cincinnati in 1830 at the age of 23. His first assignment was in Mackinac Island, Michigan and Green Bay, Wisconsin. He made several trips between these settlements in order to instruct both the white settlers and the Native Americans in the Catholic faith, and he built what would become the first Catholic church in the state of Wisconsin: St. John the Evangelist in Green Bay.

After 5 years in Mackinac and Green Bay, Fr. Mazzuchelli moved westward to the Mississippi River area of Wisconsin, Illinois, and Iowa. He ministered primarily to the Irish Catholics, who quickly adopted him as one of their own by calling him "Father Matthew Kelly." 

Fr. Mazzuchelli built several churches in this region and established many more parish communities without building churches. After a brief trip back to Italy in 1843-1844 to recover his health and write his memoirs, he returned to Wisconsin. He purchased the Sinsinawa Mound in southwest Wisconsin and there he founded schools for both men and women, and the Sinsinawa Dominican Sisters. He settled in Benton in 1849 and completed St. Patrick Church in 1852, his final church-building project. From Benton, he continued his work of preaching and teaching, this time with a congregation of sisters at his side.

On a bitterly cold day in February 1864, Fr. Mazzuchelli received a call to give Last Rites to a dying parishioner in Benton. He did not wear sufficiently warm clothing in his travels, however, and he developed pneumonia from exposure to the cold. He suffered his illness for about a week and died in his rectory in Benton on February 23, 1864 at the age of 57. He was buried in the cemetery behind St. Patrick Church. News of his untimely death spread far and wide across America, with tributes pouring in even from the coasts.

In 1964, 100 years after his death, the Diocese of Madison petitioned the Vatican to begin an investigation into the life and holiness of 
Fr. Samuel Mazzuchelli with the hopes of him being named a saint one day. This process took several years to complete, and in 1993, Pope John Paul II declared Fr. Mazzuchelli to be "Venerable." One Vatican-approved miracle attributed to his intercession is needed for him to be called "Blessed," and two are needed to name him a Saint.