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The First Presbyterian Church of Starkville, Miss., which is the oldest Presbyterian church in North Mississippi, was organized in 1821 with the Mayhew Mission to the Choctaw Indians. The mission was begun by missionaries from Massachusetts and was located about seven miles from Starkville in Oktibbeha County. Today, an old cemetery is all that remains of the old mission grounds. Rev. Cyrus Kingsbury was the first missionary sent by the American Board of Mission in answer to a call from the Choctaw Indians. He served as the first pastor of the church.

The first physical building for the newly organized Presbyterian house of worship was located on Louisville Street, just across from the old cemetery where many of Starkville’s pioneers are buried. In 1853, the church moved to its present location at 307 University Drive. In 1911, three churches in Starkville, which were the Cumberland Presbyterian Church, the United (formerly Associate Reformed) Presbyterian Church and the "Old School" Presbyterian Church, united as Starkville Presbyterian Church. The cornerstone for the present building was laid in 1924. This beautiful building is patterned after the classical Greek style of the Parthenon in Athens. Additional structures for educational and outreach purposes have been added through the years.

The Presbyterian denomination can trace its history back to the 16th century and the Protestant Reformation. The Presbyterian Church’s heritage and follower-belief system began with the French lawyer John Calvin, whose writings crystallized much of the Reformed thinking that preceded him. Today, in affirming their faith in the "catholic" or "universal" church, Presbyterians declare their oneness in Christ with millions of people in the world today who call themselves Christians.

First Presbyterian Church of Starkville is a member of St. Andrew Presbytery, which is composed of Presbyterian churches in the northern part of Mississippi. St. Andrew Presbytery is a part of the Synod of Living Waters and the General Assembly of the Presbyterian Church of the United States of America (PCUSA). The church has a nationwide membership of more than 2.5 million people.

First Presbyterian Church is governed by Elders and a Board of Deacons (the Diaconate). Through the years the church has had special interest in and conducted a ministry to the students, faculty, and administration of Mississippi State University. With this interest in mind, the church began a childcare center as an outreach program to the community in 2000. Individuals designated as Elders Emeriti for their service have been Joe Bearden, Caroline Bennett, Mary Gene Gaston, Irl Howell, Frank Jackson, Dero Ramsey, Wilmot Thomson. Trustees are Wilmot Thomson, Dero S. Ramsey, and Jim Long.

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The Session and the Diaconate have adopted this mission statement for First Presbyterian Church - Nuturing joyful faith and compassionate service. Our desire is to call all people to a personal faith in Jesus Christ through worship, service, commitment, compassion, and evangelism so that they may know God’s grace and love. Following in the footsteps of a Godly heritage, First Presbyterian Church has a glorious future ahead.