Mark DeMoss has stepped down after a disagreement with Jerry Falwell Jr, president of Liberty, over Falwell's expression of support for Donald Trump when the Republican candidate spoke earlier this year at Liberty.
His departure throws further light on the rifts caused in the evangelical Christian community by the ascendancy of Trump.
DeMoss said he thought the endorsement was not appropriate, according to Religion News.
He said: "I hope we have not 'fallen out' over this matter. I am a Liberty graduate and have been associated with the school for nearly 40 years. Despite our differences on this endorsement, Jerry and I share a love for Liberty University."
Some individuals at Liberty University asked DeMoss to resign from the executive committee that he had chaired for many years and his name was removed from the university's list of trustees.
Liberty told Patheos in a statement: "Mark DeMoss sent an email with his resignation on Tuesday, April 26, 2016, four days after the most recent Board of Trustees meeting. He was not removed from the Board of Trustees nor did the Board of Trustees ask for his resignation."
DeMoss told Patheos that he had agreed to resign as asked, and wrote a letter "tendering my resignation from the board I had served for 25 years."
In the 2008 and 2012 campaigns, DeMoss was an adviser to Republican candidate Mitt Romney. Earlier in this campaign, he supported backed Marco Rubio.