Born in Rockbridge County, Virginia on March 26, 1780, Isaac Anderson grew up in a farming family that highly valued education. Beginning with being taught by his grandmother at home to attending Liberty Hall Academy (now Washington and Lee University) to apprenticing under his pastor, Isaac embraced his educational opportunities. In 1801, Isaac and his extended family moved to the Grassy Valley area in Knox County, Tennessee for better and cheaper land and Isaac continued his studies under Rev. Samuel Carrick. A year later, he married Flora McCampbell and built this chestnut and oak hewn-log cabin on a corner of his father's land for his growing family. Six children were born to the Andersons but only one, Samuel Hoyse Anderson, survived to adulthood.

The same year he built this cabin Isaac Anderson became the first person to be licensed as a Presbyterian minister by the Union Presbytery and he established Union Academy, commonly known as “Mr. Anderson’s Log College," on his family farm. Frequently traveling a 150-mile circuit on horseback, he was a passionate Presbyterian preacher who understood that religion was directly tied to education.

Isaac lived in this cabin and taught at his “Log College” for almost ten years before he accepted the call to New Providence Presbyterian Church in Maryville where he could “do good on the largest possible scale.” Though he had to close his school, he continued to privately teach students such as Sam Houston, later Governor of both Tennessee and Texas, and former slave George Erskine, one of the first ordained African American Presbyterian ministers. Moved by the religious destitution of the region, Isaac Anderson saw the pressing need for educated ministers to evangelize the frontier. No such ministers offered themselves to his cause, so, in 1819, Isaac Anderson founded the Southern and Western Theological Seminary (later known as Maryville College) near his home on Pistol Creek in Maryville. This location is approximately where Preservation Plaza and the Founders Lot is located in downtown Maryville today.

The first student at the infant seminary was a former bootmaker's apprentice from New Hampshire named Eli Sawtell who walked to Tennessee to study under Isaac Anderson. He was the first of a long line of ministers educated at the Seminary and later Maryville College. As not all who wished to study for the ministry had the educational background to do so, preparatory classes were offered from the beginning. As the number of theological students enrolled dropped due to the establishment of other seminaries, the institution was chartered as Maryville College in 1842 to expand on the collegiate courses offered. Anderson continued to serve as President and Professor of Didactic and Polemic Theology until his death.

Tragedy struck the night of March 17, 1856 when Dr. Anderson's home burned to the ground. Awakened by the smoke and flames, Anderson's granddaughter Rebecca Anderson woke her grandfather and younger brother who were sleeping in another room. College students helped carry Dr. Anderson out of the house but were unable to quench the fire. Reportedly, Dr. Anderson's only words were "My library is burned up!" Not only did he loose his life's work but the College also lost all its early administrative papers. Following the fire, Isaac Anderson lived with is daughter-in-law's family until his death on January 28, 1857.