Newberry's heritage began in 1828 at the annual meeting of the Lutheran Synod in South Carolina and Adjacent States—nearly 30 years before it was chartered as a college by the State of South Carolina. At that 1828 meeting, the Rev. John Bachman, President of the Synod, recommended the establishment of a seminary to train Lutheran ministers. The following year the Synod followed his advice and voted to establish a seminary and classical academy. 

The new seminary-academy opened its doors in February 1831 near Pomaria, SC (about 15 miles from the College's present location); it moved to neighboring Lexington in 1834 and remained there for over 20 years. 

In 1854 the Synod voted to make the institution a degree-granting college, in 1855 to move it to Newberry, and in 1856, just before the granting of the charter, to name it Newberry College. A preparatory department opened in 1858, and the College and Seminary began operation in February 1859. 

It prospered until the Civil War when nearly all the faculty and students were called into military service. At the end of the war, the only college building was occupied by federal troops. In 1868, as a result of the physical condition of the building, the military occupation, and the depletion of the endowment funds, the College faced a severe financial crisis. St. John's Lutheran church in Walhalla, SC, in the northwestern corner of the state, offered the College a new home. In 1877, through the efforts of Newberry residents, the College returned to its original site in Newberry. 

The Synod discontinued operating the Seminary for several years, but in 1884 reopened it again at Newberry where it remained until 1898. That year the Seminary moved to Mt. Pleasant, SC, and in 1911 to its present location in Columbia, SC. 

The College has maintained its association with the Lutheran Church. Today, Newberry is affiliated with the South Carolina, Southeastern, Florida-Bahamas, and Caribbean Synods of the Evangelical Lutheran Church of America (ELCA).