Beginning in the late 19th century, League City's Catholic residents gathered in homes for Mass and other services. As the population grew, so did the need for a church. J.C. League deeded land to the Diocese of Galveston, and parishioners of St. Mary Mission Church built a frame sanctuary that served them for many years after its dedication in December 1910. The Diocese appointed the Rev. Jerome A. Rapp (1881-1952), who conducted Mass for the Catholic residents before 1910, as the mission church's first pastor. He served both this church and other mainland missions.
St. Mary Mission Church served as a social center of the community from early in its history. During the Great Depression, the church began the Mainland Catholic Picnic as a means of reducing debt. It quickly became a popular community-wide activity, lasting for many years.
As the decades passed, the League City congregation continued to grow, especially as the nearby Johnson Space Center rapidly expanded during the latter twentieth century. The church moved into a new and larger building, dedicating it in 1966. Meanwhile, the old mission was used only occasionally for church functions, although several organizations, including the Knights of Columbus, often met there.
In the late twentieth century, parishioners organized to relocate and restore the former mission church building. Today, the Gothic Revival structure is the only extant example of the original mainland missions.