A Baptist revival was held on the banks of Salado Creek as early as 1854. By about 1860, members of area Baptist, Methodist, Presbyterian and Church of Christ denominations were meeting in an ecumenical house of worship. Each group held an all-day service on successive Sundays.
On May 25, 1864, eleven men and women organized the Salado Baptist Church of Christ in the chapel of Salado College. Charter members of this group, later renamed First Baptist Church of Salado, were James L. Smith, David Hair, Harvey Chamberlain, Nannie Reed, Nellie Wemott, Sarah Hanford, Rachel Austin, Eva Cockrill, Mary L. Cearnals, Nannie Wilkinson and Sallie Wilkinson. A training union for young people soon followed. There were 19 additional members by June 1864 and 111 members by 1877. A two-story church and Masonic hall on the north bank of Salado Creek near Main Street was erected in 1878 on land donated by Bell County pioneer and church member O. T. Tyler. Two years later, an ecumenical tabernacle was erected behind the church.
The Baptist congregation sent missionaries C. Z and Kate (Crawford) Taylor to Brazil in 1881. The Ladies' Aid Society, later the Women's Missionary Union and then the Women's Ministry, was organized in 1889. This work continued in the 20th century, marked by the beginning of the ministry to Mary Hardin-Baylor College in nearby Belton in 1958. Notable members of the First Baptist Church of Salado include George W. Baines (the great-grandfather of President Lyndon B. Johnson) who served as pastor and was later president of Mary Hardin-Baylor. Others were educators at Salado College and beloved community members.