The beginning of the Church of Christ in Oxford can be traced back to the beginnings of the Civil War, when Thomas W. Caskey, a pioneer gospel preacher, was in charge of the Confederate hospital on the Ole Miss campus. The Oak Grove church in Lafayette County began in 1889, and congregations met in Pine Grove and Toccopola before the turn of the twentieth century.

There is no record of the church meeting regularly in Oxford prior to 1929. In the summer of that year, several Christians attending the University of Mississippi began meeting in the  YMCA building where the Croft Institute is currently housed. After the close of summer school the group continued to meet in the home of A. S. Huggins in Oxford. Later, the church met in a second story room on the Oxford square. In the late 1930s the congregation purchased a house on the corner of Jackson Avenue and North 14th Street and converted it into a meeting place and apartment for the minister. Their attendance averaged about 25 in 1944, and their average contribution was $12 per week. This property was sold in 1950 and land was purchased on North Lamar to construct a meeting place, now the fellowship hall. The first service in the new building was conducted on March 18, 1951. The members purchased the pews individually and did much of the finishing work. There were about 100 members. Major additions to the building were constructed in 1966 (classroom wing) and 1983 (new auditorium).

The Oxford church of Christ is multi-racial, multi-ethnic and multi-cultural, and has been so since at least the early 1980s. Other good works supported by the congregation through the years include a bus program for bringing children to Bible school and worship, sponsorship of full-time missionaries to Southern Africa and Argentina, providing space for a Korean congregation, support of a preacher training program in Guatemala, outreach to International students and visitors, and an outstanding annual Vacation Bible School. For many years, members of the congregation cleaned the building each week to free up funds for outreach and benevolence. In more recent years, efforts within the community include prison ministry, racial reconciliation, community benevolence, tutoring schoolchildren, and addiction recovery.

Since 1960, a major part of the Oxford church’s work is the campus ministry, or “Rebels for Christ.” The physical location for this work is the Alpha Omega (AΩ ) Christian Student Center at 409 Jackson Avenue, West, just across the street from the Ole Miss campus. The AΩ Center offers housing and meals. Additionally, a full-time campus minister assisted by student apprentices and interns spiritually feed about 75 students. A strong synergy has developed between short-term missions to Haiti and the campus ministry.