The first Mass was celebrated in DuBois by Fr. James Brennan at a log cabin house owned by Patrick Burns in February 1875. He returned in March 1875 to establish a mission, continuing to celebrate Mass twice a month for the next two years in homes and halls in DuBois. In 1877 St. Catherine of Siena was established as a parish. The first church was built at corner of S. State Street and Clinton Alley, costing $2500. In November 1888, Fr. Bernard McGivney became pastor. A wooden frame convent was established for six Sisters of Mercy. St. Catherine School opened on October 21, 1889 in the church basement with eight grades and 250 students.

On May 8, 1892 Bishop Tobias Mullen lays the cornerstone of the new church. He dedicates the church on September 8, 1893. Construction of a three-story school building began in 1898 to 1900. In the summer of 1909 the church steeple was struck by lightning and the fire destroys the upper portion and church interior. The church is rebuilt and rededicated in 1910.

In 1915 St. Catherine High School becomes the first accredited parochial school in the State of Pennsylvania. Saint Catherine High School closes in 1961. Central Christian High School opens its doors for the first time in September 1961.

Msgr. Bernard McGivney retires in September 1919 and is succeeded by Fr. Michael Macken. In November 1929, Fr. Maurice O’Hern is named pastor. He is succeeded by his brother, Fr. Will O’Hern in August 1936. He is pastor until March 1954 when Fr. Paul Gooder becomes the sixth pastor. In August 1978, Fr. Ernest Daley is named pastor and remains until Fr. Robert Brugger is assigned in August 1983. Fr. Richard Siefer is appointed pastor in May 1991 and continues as pastor.

Saint Catherine Church was renovated between October 1993 ad April 1994. The parish community reentered the renovated church on Easter Sunday 1994.